Rheumatology

  • Article
    | Open Access

    Intestinal dysbiosis is associated with an ever-growing list of autoimmune diseases. Here the authors show that both mice and humans with autoimmune arthritis can have dysbiosis and barrier leakiness prior to major signs of inflammatory arthritis, and treatment of mice with a zonulin antagonist can limit collagen-induced arthritis.

    • Narges Tajik
    • , Michael Frech
    • , Oscar Schulz
    • , Fabian Schälter
    • , Sébastien Lucas
    • , Vugar Azizov
    • , Kerstin Dürholz
    • , Franziska Steffen
    • , Yasunori Omata
    • , Andreas Rings
    • , Marko Bertog
    • , Aroldo Rizzo
    • , Aida Iljazovic
    • , Marijana Basic
    • , Arnd Kleyer
    • , Stephan Culemann
    • , Gerhard Krönke
    • , Yubin Luo
    • , Klaus Überla
    • , Udo S. Gaipl
    • , Benjamin Frey
    • , Till Strowig
    • , Kerstin Sarter
    • , Stephan C. Bischoff
    • , Stefan Wirtz
    • , Juan D. Cañete
    • , Francesco Ciccia
    • , Georg Schett
    •  & Mario M. Zaiss
  • Article
    | Open Access

    Moderate consumption of alcohol is associated with protection from some autoimmune diseases. Here the authors show that ethanol and its metabolite acetate can protect mice from collagen-induced arthritis and provide evidence that the mechanism of this effect might be via inhibition of the effector function of T follicular helper cells.

    • Vugar Azizov
    • , Katharina Dietel
    • , Franziska Steffen
    • , Kerstin Dürholz
    • , Julia Meidenbauer
    • , Sébastien Lucas
    • , Michael Frech
    • , Yasunori Omata
    • , Narges Tajik
    • , Lisa Knipfer
    • , Anne Kolenbrander
    • , Silvia Seubert
    • , Dennis Lapuente
    • , Maria V. Sokolova
    • , Jörg Hofmann
    • , Matthias Tenbusch
    • , Andreas Ramming
    • , Ulrike Steffen
    • , Falk Nimmerjahn
    • , Ralf Linker
    • , Stefan Wirtz
    • , Martin Herrmann
    • , Vladimir Temchura
    • , Kerstin Sarter
    • , Georg Schett
    •  & Mario M. Zaiss
  • Article
    | Open Access

    Scavenger receptor-A (SR-A) is mostly expressed by myeloid cells and has been attributed a variety of biological functions. Here the authors assess SR-A as a biomarker for diagnosis of rheumatoid arthritis (RA) using large-scale training and validation cohorts and show that modulating SR-A levels can alter progression of collagen-induced arthritis in mice.

    • Fanlei Hu
    • , Xiang Jiang
    • , Chunqing Guo
    • , Yingni Li
    • , Shixian Chen
    • , Wei Zhang
    • , Yan Du
    • , Ping Wang
    • , Xi Zheng
    • , Xiangyu Fang
    • , Xin Li
    • , Jing Song
    • , Yang Xie
    • , Fei Huang
    • , Jimeng Xue
    • , Mingxin Bai
    • , Yuan Jia
    • , Xu Liu
    • , Limin Ren
    • , Xiaoying Zhang
    • , Jianping Guo
    • , Hudan Pan
    • , Yin Su
    • , Huanfa Yi
    • , Hua Ye
    • , Daming Zuo
    • , Juan Li
    • , Huaxiang Wu
    • , Yongfu Wang
    • , Ru Li
    • , Liang Liu
    • , Xiang-Yang Wang
    •  & Zhanguo Li
  • Article
    | Open Access

    Systemic lupus erythematosus (SLE) is an autoimmune disorder which can have neurological manifestations, including autoantibody targeting of the NMDA receptor. In this study, the authors GluN2A subunit is a target of SLE autoantibodies, using sample derived from patient.

    • Kelvin Chan
    • , Jacquelyn Nestor
    • , Tomás S. Huerta
    • , Noele Certain
    • , Gabrielle Moody
    • , Czeslawa Kowal
    • , Patricio T. Huerta
    • , Bruce T. Volpe
    • , Betty Diamond
    •  & Lonnie P. Wollmuth
  • Article
    | Open Access

    Fibroblast hyper-activation and proliferation is a major feature in arthritis, yet scarcely addressed for anti-arthritic therapies. Here, the authors show that activation of the MC1 receptor induces fibroblast senescence associated with a reparative phenotype, ultimately regulating experimental inflammatory arthritis.

    • Trinidad Montero-Melendez
    • , Ai Nagano
    • , Claude Chelala
    • , Andrew Filer
    • , Christopher D. Buckley
    •  & Mauro Perretti
  • Article
    | Open Access

    Multinucleated giant cells (MGCs) are important in the pathogenesis of various diseases. Here, the authors demonstrate that extracellular presence of the amino acid arginine is required for MGC formation and metabolism, suggesting a translational impact for strategies utilizing systemic arginine depletion in MGC-mediated diseases.

    • Julia S. Brunner
    • , Loan Vulliard
    • , Melanie Hofmann
    • , Markus Kieler
    • , Alexander Lercher
    • , Andrea Vogel
    • , Marion Russier
    • , Johanna B. Brüggenthies
    • , Martina Kerndl
    • , Victoria Saferding
    • , Birgit Niederreiter
    • , Alexandra Junza
    • , Annika Frauenstein
    • , Carina Scholtysek
    • , Yohei Mikami
    • , Kristaps Klavins
    • , Gerhard Krönke
    • , Andreas Bergthaler
    • , John J. O’Shea
    • , Thomas Weichhart
    • , Felix Meissner
    • , Josef S. Smolen
    • , Paul Cheng
    • , Oscar Yanes
    • , Jörg Menche
    • , Peter J. Murray
    • , Omar Sharif
    • , Stephan Blüml
    •  & Gernot Schabbauer
  • Article
    | Open Access

    Spondyloarthritis pathology is manifested by increased myeloid infiltration of the joints. Here the authors show that in a mouse model of spondyloarthritis, a single dose of a microbial ligand curdlan induces persistent extramedullary myelopoiesis in the spleen and joints, which is driven by GM-CSF and can be amplified by exogenous IL-33.

    • Daniel Regan-Komito
    • , James W. Swann
    • , Philippos Demetriou
    • , E. Suzanne Cohen
    • , Nicole J. Horwood
    • , Stephen N. Sansom
    •  & Thibault Griseri
  • Article
    | Open Access

    Immunoglobulin A (IgA) has two subclasses, IgA1 and IgA2, but differential effects on inflammation are unclear. Here the authors show that IgA2, when compared with IgA1, has stronger pro-inflammatory functions associated with changed glycosylation and higher disease scores in patients with rheumatoid arthritis.

    • Ulrike Steffen
    • , Carolien A. Koeleman
    • , Maria V. Sokolova
    • , Holger Bang
    • , Arnd Kleyer
    • , Jürgen Rech
    • , Harald Unterweger
    • , Martin Schicht
    • , Fabian Garreis
    • , Jonas Hahn
    • , Fabian T. Andes
    • , Fabian Hartmann
    • , Madelaine Hahn
    • , Aparna Mahajan
    • , Friedrich Paulsen
    • , Markus Hoffmann
    • , Günter Lochnit
    • , Luis E. Muñoz
    • , Manfred Wuhrer
    • , David Falck
    • , Martin Herrmann
    •  & Georg Schett
  • Article
    | Open Access

    Skewing of X chromosome inactivation (XCI) occurs when the silencing of one parental X chromosome is non-random. Here, Zito et al. report XCI patterns in lymphoblastoid cell lines, blood, subcutaneous adipose tissue samples and skin samples of monozygotic and dizygotic twins and find XCI skew to associate with tissue and age.

    • Antonino Zito
    • , Matthew N. Davies
    • , Pei-Chien Tsai
    • , Susanna Roberts
    • , Rosa Andres-Ejarque
    • , Stefano Nardone
    • , Jordana T. Bell
    • , Chloe C. Y. Wong
    •  & Kerrin S. Small
  • Article
    | Open Access

    Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).

    • Paul A Lyons
    • , James E Peters
    • , Federico Alberici
    • , James Liley
    • , Richard M. R. Coulson
    • , William Astle
    • , Chiara Baldini
    • , Francesco Bonatti
    • , Maria C Cid
    • , Heather Elding
    • , Giacomo Emmi
    • , Jörg Epplen
    • , Loïc Guillevin
    • , David R. W. Jayne
    • , Tao Jiang
    • , Iva Gunnarsson
    • , Peter Lamprecht
    • , Stephen Leslie
    • , Mark A. Little
    • , Davide Martorana
    • , Frank Moosig
    • , Thomas Neumann
    • , Sophie Ohlsson
    • , Stefanie Quickert
    • , Giuseppe A. Ramirez
    • , Barbara Rewerska
    • , Georg Schett
    • , Renato A. Sinico
    • , Wojciech Szczeklik
    • , Vladimir Tesar
    • , Damjan Vukcevic
    • , Mohammed Akil
    • , Jonathan Barratt
    • , Neil Basu
    • , Adam S. Butterworth
    • , Ian Bruce
    • , Michael Clarkson
    • , Niall Conlon
    • , Bhaskar DasGupta
    • , Timothy W. R. Doulton
    • , Georgina Espígol-Frigolé
    • , Oliver Flossmann
    • , Armando Gabrielli
    • , Jolanta Gasior
    • , Gina Gregorini
    • , Giuseppe Guida
    • , José Hernández-Rodríguez
    • , Zdenka Hruskova
    • , Amy Hudson
    • , Ann Knight
    • , Peter Lanyon
    • , Raashid Luqmani
    • , Malgorzata Magliano
    • , Angelo A. Manfredi
    • , Christopher Marguerie
    • , Federica Maritati
    • , Chiara Marvisi
    • , Neil J. McHugh
    • , Eamonn Molloy
    • , Allan Motyer
    • , Chetan Mukhtyar
    • , Leonid Padyukov
    • , Alberto Pesci
    • , Sergio Prieto-Gonzalez
    • , Marc Ramentol-Sintas
    • , Petra Reis
    • , Dario Roccatello
    • , Patrizia Rovere-Querini
    • , Carlo Salvarani
    • , Francesca Santarsia
    • , Roser Solans-Laque
    • , Nicole Soranzo
    • , Jo Taylor
    • , Julie Wessels
    • , Jochen Zwerina
    • , Benjamin Terrier
    • , Richard A Watts
    • , Augusto Vaglio
    • , Julia U Holle
    • , Chris Wallace
    •  & Kenneth G. C. Smith
  • Article
    | Open Access

    Systemic sclerosis (SSc) is a heterogeneous chronic autoimmune disease that affects the connective tissue. Here, López-Isac et al. identify 13 new risk loci for SSc as well as loci specific for limited cutaneous and diffuse SSc and, defining credible sets and performing functional annotation, highlight key pathways and cell types for SSc.

    • Elena López-Isac
    • , Marialbert Acosta-Herrera
    • , Martin Kerick
    • , Shervin Assassi
    • , Ansuman T. Satpathy
    • , Jeffrey Granja
    • , Maxwell R. Mumbach
    • , Lorenzo Beretta
    • , Carmen P. Simeón
    • , Patricia Carreira
    • , Norberto Ortego-Centeno
    • , Ivan Castellvi
    • , Lara Bossini-Castillo
    • , F. David Carmona
    • , Gisela Orozco
    • , Nicolas Hunzelmann
    • , Jörg H. W. Distler
    • , Andre Franke
    • , Claudio Lunardi
    • , Gianluca Moroncini
    • , Armando Gabrielli
    • , Jeska de Vries-Bouwstra
    • , Cisca Wijmenga
    • , Bobby P. C. Koeleman
    • , Annika Nordin
    • , Leonid Padyukov
    • , Anna-Maria Hoffmann-Vold
    • , Benedicte Lie
    • , R. Ríos
    • , J. L. Callejas
    • , J. A. Vargas-Hitos
    • , R. García-Portales
    • , M. T. Camps
    • , A. Fernández-Nebro
    • , M. F. González-Escribano
    • , F. J. García-Hernández
    • , M. J. Castillo
    • , M. A. Aguirre
    • , I. Gómez-Gracia
    • , B. Fernández-Gutiérrez
    • , L. Rodríguez-Rodríguez
    • , P. García de la Peña
    • , E. Vicente
    • , J. L. Andreu
    • , M Fernández de Castro
    • , F. J. López-Longo
    • , L. Martínez
    • , Fonollosa V
    • , A. Guillén
    • , G. Espinosa
    • , C. Tolosa
    • , A. Pros
    • , M. Rodríguez-Carballeira
    • , F. J. Narváez
    • , M. Rubio-Rivas
    • , Ortiz-Santamaría V
    • , A. B. Madroñero
    • , M. A. González-Gay
    • , B. Díaz
    • , L. Trapiella
    • , A. Sousa
    • , M. V. Egurbide
    • , P. Fanlo-Mateo
    • , L. Sáez-Comet
    • , F. Díaz
    • , Hernández V
    • , E. Beltrán
    • , J. A. Román-Ivorra
    • , E. Grau
    • , J. J. Alegre-Sancho
    • , M. Freire
    • , F. J. Blanco-García
    • , N. Oreiro
    • , T. Witte
    • , A. Kreuter
    • , G. Riemekasten
    • , P. Airó
    • , C. Magro
    • , A. E. Voskuyl
    • , M. C. Vonk
    • , R. Hesselstrand
    • , Susanna Proudman
    • , Wendy Stevens
    • , Mandana Nikpour
    • , J. Zochling
    • , J. Sahhar
    • , J. Roddy
    • , P. Nash
    • , K. Tymms
    • , M. Rischmueller
    • , S. Lester
    • , Timothy Vyse
    • , Ariane L. Herrick
    • , Jane Worthington
    • , Christopher P. Denton
    • , Yannick Allanore
    • , Matthew A. Brown
    • , Timothy R. D. J. Radstake
    • , Carmen Fonseca
    • , Howard Y. Chang
    • , Maureen D. Mayes
    •  & Javier Martin
  • Article
    | Open Access

    Alterations to the microbiome are now associated with various diseases. Here the authors analyze microbiomes from a large population based cohort and show positive correlations between abundance of Streptococcus spp. and osteoarthritis-related knee pain.

    • Cindy G. Boer
    • , Djawad Radjabzadeh
    • , Carolina Medina-Gomez
    • , Sanzhima Garmaeva
    • , Dieuwke Schiphof
    • , Pascal Arp
    • , Thomas Koet
    • , Alexander Kurilshikov
    • , Jingyuan Fu
    • , M. Arfan Ikram
    • , Sita Bierma-Zeinstra
    • , André G. Uitterlinden
    • , Robert Kraaij
    • , Alexandra Zhernakova
    •  & Joyce B. J. van Meurs
  • Article
    | Open Access

    Interleukin-7 (IL-7) is a central cytokine in T cell homeostasis. Here the authors show that allelic variation at rs6897932, an autoimmune GWAS risk allele at IL7R, regulates surface and soluble IL-7R in stimulated monocytes, indicating a function of monocytes in IL-7-related autoimmunity.

    • Hussein Al-Mossawi
    • , Nicole Yager
    • , Chelsea A. Taylor
    • , Evelyn Lau
    • , Sara Danielli
    • , Jelle de Wit
    • , James Gilchrist
    • , Isar Nassiri
    • , Elise A. Mahe
    • , Wanseon Lee
    • , Laila Rizvi
    • , Seiko Makino
    • , Jane Cheeseman
    • , Matt Neville
    • , Julian C. Knight
    • , Paul Bowness
    •  & Benjamin P. Fairfax
  • Article
    | Open Access

    Systemic lupus erythematosus (SLE) is an autoimmune disease of substantial phenotypic heterogeneity in different ethnic groups. Here, using data from a multi-ethnic cohort, the authors describe an approach based on clinical and molecular data to subtype SLE patients into three clusters of severity.

    • Cristina M. Lanata
    • , Ishan Paranjpe
    • , Joanne Nititham
    • , Kimberly E. Taylor
    • , Milena Gianfrancesco
    • , Manish Paranjpe
    • , Shan Andrews
    • , Sharon A. Chung
    • , Brooke Rhead
    • , Lisa F. Barcellos
    • , Laura Trupin
    • , Patricia Katz
    • , Maria Dall’Era
    • , Jinoos Yazdany
    • , Marina Sirota
    •  & Lindsey A. Criswell
  • Article
    | Open Access

    Autoreactivity to myeloperoxidase (MPO) causes autoimmune vasculitis and severe glomerulonephritis. Here, Ooi et al. show that a Staphylococcus aureus plasmid encodes a peptide that is homologous to an immunodominant MPO epitope and induces anti-MPO autoimmunity and glomerulonephritis in mice.

    • Joshua D. Ooi
    • , Jhih-Hang Jiang
    • , Peter J. Eggenhuizen
    • , Ling L. Chua
    • , Mirjan van Timmeren
    • , Khai L. Loh
    • , Kim M. O’Sullivan
    • , Poh Y. Gan
    • , Yong Zhong
    • , Kirill Tsyganov
    • , Lani R. Shochet
    • , Jessica Ryan
    • , Coen A. Stegeman
    • , Lars Fugger
    • , Hugh H. Reid
    • , Jamie Rossjohn
    • , Peter Heeringa
    • , Stephen R. Holdsworth
    • , Anton Y. Peleg
    •  & A. Richard Kitching
  • Article
    | Open Access

    Promising pilot clinical trials of mesenchymal stem cells (MSCs) therapy of lupus await validation in larger, controlled trials. Here the authors show that MSCs expand CD1c+ dendritic cells in cell culture by producing FLT3L, and that in lupus patients, circulating CD1c+ dendritic cells and FLT3L are increased following MSCs therapy.

    • Xinran Yuan
    • , Xiaodong Qin
    • , Dandan Wang
    • , Zhuoya Zhang
    • , Xiaojun Tang
    • , Xiang Gao
    • , Wanjun Chen
    •  & Lingyun Sun
  • Article
    | Open Access

    Size and shape of bones are important for height and body shape. Here, Styrkarsdottir et al identify 12 loci in a GWAS for bone area derived from DXA scans and show that these loci associate with other bone-related phenotypes including osteoarthritis, height, bone mineral density and risk of hip fracture.

    • Unnur Styrkarsdottir
    • , Olafur A. Stefansson
    • , Kristbjorg Gunnarsdottir
    • , Gudmar Thorleifsson
    • , Sigrun H. Lund
    • , Lilja Stefansdottir
    • , Kristinn Juliusson
    • , Arna B. Agustsdottir
    • , Florian Zink
    • , Gisli H. Halldorsson
    • , Erna V. Ivarsdottir
    • , Stefania Benonisdottir
    • , Hakon Jonsson
    • , Arnaldur Gylfason
    • , Kristjan Norland
    • , Katerina Trajanoska
    • , Cindy G. Boer
    • , Lorraine Southam
    • , Jason C. S. Leung
    • , Nelson L. S. Tang
    • , Timothy C. Y. Kwok
    • , Jenny S. W. Lee
    • , Suzanne C. Ho
    • , Inger Byrjalsen
    • , Jacqueline R. Center
    • , Seung Hun Lee
    • , Jung-Min Koh
    • , L. Stefan Lohmander
    • , Lan T. Ho-Pham
    • , Tuan V. Nguyen
    • , John A. Eisman
    • , Jean Woo
    • , Ping-C. Leung
    • , John Loughlin
    • , Eleftheria Zeggini
    • , Claus Christiansen
    • , Fernando Rivadeneira
    • , Joyce van Meurs
    • , Andre G. Uitterlinden
    • , Brynjolfur Mogensen
    • , Helgi Jonsson
    • , Thorvaldur Ingvarsson
    • , Gunnar Sigurdsson
    • , Rafn Benediktsson
    • , Patrick Sulem
    • , Ingileif Jonsdottir
    • , Gisli Masson
    • , Hilma Holm
    • , Gudmundur L. Norddahl
    • , Unnur Thorsteinsdottir
    • , Daniel F. Gudbjartsson
    •  & Kari Stefansson
  • Article
    | Open Access

    CXCL4 is an inflammatory chemokine signaling through CXCR3 receptor. Here the authors show a CXCR3-independent function of CXCL4: it forms liquid crystals with DNA, potentiating mammalian and bacterial DNA recognition by TLR9, thereby amplifying interferon-a production in systemic sclerosis.

    • Roberto Lande
    • , Ernest Y. Lee
    • , Raffaella Palazzo
    • , Barbara Marinari
    • , Immacolata Pietraforte
    • , Giancarlo Santiago Santos
    • , Yves Mattenberger
    • , Francesca Spadaro
    • , Katia Stefanantoni
    • , Nicoletta Iannace
    • , Aleksandra Maria Dufour
    • , Mario Falchi
    • , Manuela Bianco
    • , Elisabetta Botti
    • , Luca Bianchi
    • , Montserrat Alvarez
    • , Valeria Riccieri
    • , Marie-Elise Truchetet
    • , Gerard C.L. Wong
    • , Carlo Chizzolini
    •  & Loredana Frasca
  • Article
    | Open Access

    Loss of cartilage tissue is a hallmark of osteoarthritis. Here the authors show that BNTA, a small molecule identified in a chemical screen, promotes ECM generation in human osteoarthritic chondrocytes and cartilage explants, and suppresses pathology in a rat model of osteoarthritis.

    • Yuanyuan Shi
    • , Xiaoqing Hu
    • , Jin Cheng
    • , Xin Zhang
    • , Fengyuan Zhao
    • , Weili Shi
    • , Bo Ren
    • , Huilei Yu
    • , Peng Yang
    • , Zong Li
    • , Qiang Liu
    • , Zhenlong Liu
    • , Xiaoning Duan
    • , Xin Fu
    • , Jiying Zhang
    • , Jianquan Wang
    •  & Yingfang Ao
  • Article
    | Open Access

    GWAS have identified numerous genetic loci for bone mineral density (BMD) and fracture risk. Here, the authors map these variants to putative target genes using ATAC-seq and Capture C of human osteoblasts and confirm ING3 and EPDR1 as BMD genes in in vitro osteoblast differentiation experiments.

    • Alessandra Chesi
    • , Yadav Wagley
    • , Matthew E. Johnson
    • , Elisabetta Manduchi
    • , Chun Su
    • , Sumei Lu
    • , Michelle E. Leonard
    • , Kenyaita M. Hodge
    • , James A. Pippin
    • , Kurt D. Hankenson
    • , Andrew D. Wells
    •  & Struan F. A. Grant
  • Article
    | Open Access

    Modulation of the cholinergic pathway and spleen function can reduce inflammation with invasive implants. Here, the authors show that non-invasive ultrasound stimulation of the spleen reduces disease severity in a mouse model of inflammatory arthritis, partly via altering B and T cell function.

    • Daniel P. Zachs
    • , Sarah J. Offutt
    • , Rachel S. Graham
    • , Yohan Kim
    • , Jerel Mueller
    • , Jennifer L. Auger
    • , Nathaniel J. Schuldt
    • , Claire R. W. Kaiser
    • , Abigail P. Heiller
    • , Raini Dutta
    • , Hongsun Guo
    • , Jamu K. Alford
    • , Bryce A. Binstadt
    •  & Hubert H. Lim
  • Article
    | Open Access

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    • , Jack A Bibby
    • , Wing Wu
    • , Klaus Stensgaard Frederiksen
    • , Ceri A. Roberts
    • , Zoe Hall
    • , Gaelle LeFriec
    • , Kevin A. Robertson
    • , Paul Lavender
    • , Jens Gammeltoft Gerwien
    • , Leonie S. Taams
    • , Julian L. Griffin
    • , Emanuele de Rinaldis
    • , Lisa G. M. van Baarsen
    • , Claudia Kemper
    • , Peter Ghazal
    •  & Andrew P. Cope
  • Article
    | Open Access

    Bone is innervated, and its turnover is affected by sympathetic nerve activity. Here, the authors show that prostaglandin E2, secreted by osteoblasts, activates the EP4 receptor on sensory nerves, inhibiting sympathetic nerve activity and modulating bone formation in mice.

    • Hao Chen
    • , Bo Hu
    • , Xiao Lv
    • , Shouan Zhu
    • , Gehua Zhen
    • , Mei Wan
    • , Amit Jain
    • , Bo Gao
    • , Yu Chai
    • , Mi Yang
    • , Xiao Wang
    • , Ruoxian Deng
    • , Lei Wang
    • , Yong Cao
    • , Shuangfei Ni
    • , Shen Liu
    • , Wen Yuan
    • , Huajiang Chen
    • , Xinzhong Dong
    • , Yun Guan
    • , Huilin Yang
    •  & Xu Cao
  • Article
    | Open Access

    The role of innate T cell subsets in the pathogenesis of spondyloarthritis (SpA) is not well understood. Here, the authors examine the role of invariant natural killer T (iNKT) and γδ-T cells in SpA and show that disease-derived iNKT and γδ-T cells have unique and Th17-skewed phenotype and gene expression profiles within inflamed joints.

    • Koen Venken
    • , Peggy Jacques
    • , Céline Mortier
    • , Mark E. Labadia
    • , Tine Decruy
    • , Julie Coudenys
    • , Kathleen Hoyt
    • , Anita L. Wayne
    • , Robert Hughes
    • , Michael Turner
    • , Sofie Van Gassen
    • , Liesbet Martens
    • , Dustin Smith
    • , Christian Harcken
    • , Joseph Wahle
    • , Chao-Ting Wang
    • , Eveline Verheugen
    • , Nadia Schryvers
    • , Gaëlle Varkas
    • , Heleen Cypers
    • , Ruth Wittoek
    • , Yves Piette
    • , Lieve Gyselbrecht
    • , Serge Van Calenbergh
    • , Filip Van den Bosch
    • , Yvan Saeys
    • , Gerald Nabozny
    •  & Dirk Elewaut
  • Article
    | Open Access

    Pro-inflammatory factors implicated for the onset of arthritis often have systematic effects, yet arthritis symptoms are mostly limited to the joints. Here the authors show that mechanical strain at the joints promotes the recruitment of monocyte and their differentiation into bone-eroding osteoclast to contribute this tissue specificity.

    • Isabelle Cambré
    • , Djoere Gaublomme
    • , Arne Burssens
    • , Peggy Jacques
    • , Nadia Schryvers
    • , Amélie De Muynck
    • , Leander Meuris
    • , Stijn Lambrecht
    • , Shea Carter
    • , Pieter de Bleser
    • , Yvan Saeys
    • , Luc Van Hoorebeke
    • , George Kollias
    • , Matthias Mack
    • , Paul Simoens
    • , Rik Lories
    • , Nico Callewaert
    • , Georg Schett
    •  & Dirk Elewaut
  • Article
    | Open Access

    Cell-free DNA (cfDNA) released from damaged or dead cells can activate DNA sensors that exacerbate the pathogenesis of rheumatoid arthritis (RA). Here the authors use ~40 nm cationic nanoparticles to scavenge cfDNA, and demonstrate the potential for nanomedicine to relieve debilitating RA symptoms.

    • Huiyi Liang
    • , Bo Peng
    • , Cong Dong
    • , Lixin Liu
    • , Jiaji Mao
    • , Song Wei
    • , Xinlu Wang
    • , Hanshi Xu
    • , Jun Shen
    • , Hai-Quan Mao
    • , Xiaohu Gao
    • , Kam W. Leong
    •  & Yongming Chen
  • Article
    | Open Access

    Approximately 30% of psoriasis patients develop psoriatic arthritis (PsA) and early diagnosis is crucial for the management of PsA. Here, Patrick et al. develop a computational pipeline involving statistical and machine-learning methods that can assess the risk of progression to PsA based on genetic markers.

    • Matthew T. Patrick
    • , Philip E. Stuart
    • , Kalpana Raja
    • , Johann E. Gudjonsson
    • , Trilokraj Tejasvi
    • , Jingjing Yang
    • , Vinod Chandran
    • , Sayantan Das
    • , Kristina Callis-Duffin
    • , Eva Ellinghaus
    • , Charlotta Enerbäck
    • , Tõnu Esko
    • , Andre Franke
    • , Hyun M. Kang
    • , Gerald G. Krueger
    • , Henry W. Lim
    • , Proton Rahman
    • , Cheryl F. Rosen
    • , Stephan Weidinger
    • , Michael Weichenthal
    • , Xiaoquan Wen
    • , John J. Voorhees
    • , Gonçalo R. Abecasis
    • , Dafna D. Gladman
    • , Rajan P. Nair
    • , James T. Elder
    •  & Lam C. Tsoi
  • Article
    | Open Access

    Osteoclasts mediate bone disruption in a number of degenerative bone diseases. Here, the authors show that miR-182 regulates osteoclastogenesis via PKR and IFN-beta signaling, is correlated with rheumatoid arthritis, and that its ablation or inhibition is protective against bone erosion in mouse models of osteoporosis or inflammatory arthritis.

    • Kazuki Inoue
    • , Zhonghao Deng
    • , Yufan Chen
    • , Eugenia Giannopoulou
    • , Ren Xu
    • , Shiaoching Gong
    • , Matthew B. Greenblatt
    • , Lingegowda S. Mangala
    • , Gabriel Lopez-Berestein
    • , David G. Kirsch
    • , Anil K. Sood
    • , Liang Zhao
    •  & Baohong Zhao
  • Article
    | Open Access

    Osteocytes reside in a low oxygen environment, but it is not clear if oxygen sensing regulates their function. Here, the authors show that deletion of the oxygen sensor prolyl hydroxylase 2 in osteocytes leads to increased bone mass via regulation of sclerostin, and reduces bone loss in mouse models of osteoporosis.

    • Steve Stegen
    • , Ingrid Stockmans
    • , Karen Moermans
    • , Bernard Thienpont
    • , Patrick H. Maxwell
    • , Peter Carmeliet
    •  & Geert Carmeliet
  • Article
    | Open Access

    IFN-γ is central in inflammatory pathogenesis, response to infection and autoimmune diseases. Here the authors show that MMP12 expression is reduced in patients with SLE and that MMP12 post-translationally truncates IFN-y, inhibiting its function and affecting pathogenesis of mouse models of peritonitis, SLE and rheumatoid arthritis.

    • Antoine Dufour
    • , Caroline L. Bellac
    • , Ulrich Eckhard
    • , Nestor Solis
    • , Theo Klein
    • , Reinhild Kappelhoff
    • , Nikolaus Fortelny
    • , Parker Jobin
    • , Jacob Rozmus
    • , Jennifer Mark
    • , Paul Pavlidis
    • , Vincent Dive
    • , Sean J. Barbour
    •  & Christopher M. Overall
  • Article
    | Open Access

    Many diseases, such as rheumatoid arthritis, are characterized by a chronic inflammatory state, but it is not clear whether or how this affects the brain. Here, the authors show that the severity of on-going inflammation predicts altered functional brain connectivity in people with rheumatoid arthritis.

    • Andrew Schrepf
    • , Chelsea M. Kaplan
    • , Eric Ichesco
    • , Tony Larkin
    • , Steven E. Harte
    • , Richard E. Harris
    • , Alison D. Murray
    • , Gordon D. Waiter
    • , Daniel J. Clauw
    •  & Neil Basu
  • Article
    | Open Access

    Fibroblast-like synoviocytes (FLS) in the intimal layer of the synovium can become invasive and destroy cartilage in patients with rheumatoid arthritis (RA). Here the authors integrate a variety of epigenomic data to map the epigenome of FLS in RA and identify potential therapeutic targets.

    • Rizi Ai
    • , Teresina Laragione
    • , Deepa Hammaker
    • , David L. Boyle
    • , Andre Wildberg
    • , Keisuke Maeshima
    • , Emanuele Palescandolo
    • , Vinod Krishna
    • , David Pocalyko
    • , John W. Whitaker
    • , Yuchen Bai
    • , Sunil Nagpal
    • , Kurtis E. Bachman
    • , Richard I. Ainsworth
    • , Mengchi Wang
    • , Bo Ding
    • , Percio S. Gulko
    • , Wei Wang
    •  & Gary S. Firestein
  • Article
    | Open Access

    CXCR2 antagonism has been shown to be anti-arthritic, but anti-chemokine therapies usually fail in the clinic owing to redundancy in chemokine-receptor interactions. Here the authors develop single-chain antibodies with multiple chemokine specificities to achieve high affinity and broad specificity to mouse and human CXC chemokines with efficacy in a K/BxN serum transfer model of arthritis.

    • Alessandro Angelini
    • , Yoshishige Miyabe
    • , Daniel Newsted
    • , Byron H. Kwan
    • , Chie Miyabe
    • , Ryan L. Kelly
    • , Misha N. Jamy
    • , Andrew D. Luster
    •  & K. Dane Wittrup
  • Article
    | Open Access

    Anti-TNF therapy has improved the treatment of inflammatory disease but can predispose to infection and malignancy. Here the authors show an anti-TNF biologic peptide that functionally and selectively targets the TNF-p38 pathway in multiple models of inflammation.

    • Violet R. Mukaro
    • , Alex Quach
    • , Michelle E. Gahan
    • , Bernadette Boog
    • , Zhi H. Huang
    • , Xiuhui Gao
    • , Carol Haddad
    • , Suresh Mahalingam
    • , Charles S. Hii
    •  & Antonio Ferrante
  • Article
    | Open Access

    The treatment of inflammatory arthritis by local delivery of therapeutics is limited by short half-lives of drugs. Here the authors demonstrate a hydrogel platform that titrates drug release to arthritis activity.

    • Nitin Joshi
    • , Jing Yan
    • , Seth Levy
    • , Sachin Bhagchandani
    • , Kai V. Slaughter
    • , Nicholas E. Sherman
    • , Julian Amirault
    • , Yufeng Wang
    • , Logan Riegel
    • , Xueyin He
    • , Tan Shi Rui
    • , Michael Valic
    • , Praveen K. Vemula
    • , Oscar R. Miranda
    • , Oren Levy
    • , Ellen M. Gravallese
    • , Antonios O. Aliprantis
    • , Joerg Ermann
    •  & Jeffrey M. Karp
  • Article
    | Open Access

    Synovial fibroblasts are thought to be central mediators of joint destruction in rheumatoid arthritis (RA). Here the authors use single-cell transcriptomics and flow cytometry to identify synovial fibroblast subsets that are expanded and display distinct tissue distribution and function in patients with RA.

    • Fumitaka Mizoguchi
    • , Kamil Slowikowski
    • , Kevin Wei
    • , Jennifer L. Marshall
    • , Deepak A. Rao
    • , Sook Kyung Chang
    • , Hung N. Nguyen
    • , Erika H. Noss
    • , Jason D. Turner
    • , Brandon E. Earp
    • , Philip E. Blazar
    • , John Wright
    • , Barry P. Simmons
    • , Laura T. Donlin
    • , George D. Kalliolias
    • , Susan M. Goodman
    • , Vivian P. Bykerk
    • , Lionel B. Ivashkiv
    • , James A. Lederer
    • , Nir Hacohen
    • , Peter A. Nigrovic
    • , Andrew Filer
    • , Christopher D. Buckley
    • , Soumya Raychaudhuri
    •  & Michael B. Brenner
  • Article
    | Open Access

    TNF is a major therapeutic target for rheumatoid arthritis (RA) and synovial fibroblasts are central to the pathogenesis of RA. Here the authors dissect TNF-induced death and activation signalling in RA synovial fibroblasts and TNF-driven arthritis and indicate that a successful therapeutic strategy might be to target both IKK2 and RIPK3 at the same time.

    • Marietta Armaka
    • , Caroline Ospelt
    • , Manolis Pasparakis
    •  & George Kollias
  • Article
    | Open Access

    Th17 cells are a common pathogenic effector cell in autoimmune inflammatory diseases. Here the authors show that the transcription factor RFX1 limits Th17 differentiation and is protective against the pathogenesis of Th17-driven autoimmune diseases.

    • Ming Zhao
    • , Yixin Tan
    • , Qiao Peng
    • , Cancan Huang
    • , Yu Guo
    • , Gongping Liang
    • , Bochen Zhu
    • , Yi Huang
    • , Aiyun Liu
    • , Zijun Wang
    • , Mengying Li
    • , Xiaofei Gao
    • , Ruifang Wu
    • , Haijing Wu
    • , Hai Long
    •  & Qianjin Lu
  • Article
    | Open Access

    Osteoclasts are involved in arthritis, and their differentiation depends on RANKL signaling. The author show that the ROS-scavenging protein DJ-1 negatively regulates RANKL signaling and that its ablation increases osteoclast numbers and exacerbates bone damage in mouse models of arthritis.

    • Hyuk Soon Kim
    • , Seung Taek Nam
    • , Se Hwan Mun
    • , Sun-Kyeong Lee
    • , Hyun Woo Kim
    • , Young Hwan Park
    • , Bokyung Kim
    • , Kyung-Jong Won
    • , Hae-Rim Kim
    • , Yeong-Min Park
    • , Hyung Sik Kim
    • , Michael A. Beaven
    • , Young Mi Kim
    •  & Wahn Soo Choi
  • Article
    | Open Access

    STAT3 is a transcription factor that is activated in fibrotic diseases such as systemic sclerosis. Here the authors show that STAT3 is the converging point for multiple pro-fibrotic signalling pathways, and that its genetic ablation or inhibition ameliorate skin fibrosis in mouse models.

    • Debomita Chakraborty
    • , Barbora Šumová
    • , Tatjana Mallano
    • , Chih-Wei Chen
    • , Alfiya Distler
    • , Christina Bergmann
    • , Ingo Ludolph
    • , Raymund E. Horch
    • , Kolja Gelse
    • , Andreas Ramming
    • , Oliver Distler
    • , Georg Schett
    • , Ladislav Šenolt
    •  & Jörg H. W. Distler
  • Article
    | Open Access

    Post-translational modifications can affect antibody function in health and disease, but identification of all variants is difficult using existing technologies. Here the authors develop a microfluidic method to identify and quantify low-abundance IgG N-glycans and show some of these IgGs can be used as biomarkers for rheumatoid arthritis.

    • Jing-Rong Wang
    • , Wei-Na Gao
    • , Rudolf Grimm
    • , Shibo Jiang
    • , Yong Liang
    • , Hua Ye
    • , Zhan-Guo Li
    • , Lee-Fong Yau
    • , Hao Huang
    • , Ju Liu
    • , Min Jiang
    • , Qiong Meng
    • , Tian-Tian Tong
    • , Hai-Hui Huang
    • , Stephanie Lee
    • , Xing Zeng
    • , Liang Liu
    •  & Zhi-Hong Jiang
  • Article
    | Open Access

    Accumulation of somatic mutations in lymphocytes is a feature of some cancers. Here the authors show that patients with recent onset of rheumatoid arthritis also accumulate mutations in their expanded CD8+ effector memory T cell pool independent of cancer association.

    • P. Savola
    • , T. Kelkka
    • , H. L. Rajala
    • , A. Kuuliala
    • , K. Kuuliala
    • , S. Eldfors
    • , P. Ellonen
    • , S. Lagström
    • , M. Lepistö
    • , T. Hannunen
    • , E. I. Andersson
    • , R. K. Khajuria
    • , T. Jaatinen
    • , R. Koivuniemi
    • , H. Repo
    • , J. Saarela
    • , K. Porkka
    • , M. Leirisalo-Repo
    •  & S. Mustjoki
  • Article
    | Open Access

    DOT1L is one of the few genes linked to osteoarthritis by human GWAS. Here the authors show that DOT1L-dependent histone methylation protects homeostasis of articular chondrocytes by SIRT1-dependent inhibition of canonical WNT signalling, and that inhibition of DOT1L can drive osteoarthritic disease in mice.

    • Silvia Monteagudo
    • , Frederique M. F. Cornelis
    • , Carolina Aznar-Lopez
    • , Ploi Yibmantasiri
    • , Laura-An Guns
    • , Peter Carmeliet
    • , Frédéric Cailotto
    •  & Rik J. Lories
  • Article
    | Open Access

    Bone loss is common in patients with diabetes, but the underlying molecular and cellular mechanisms are unclear. Here the authors show high succinate levels in mice with type 2 diabetes and that succinate can signal through succinate receptor 1 on osteoclasts to induce bone resorption.

    • Yuqi Guo
    • , Chengzhi Xie
    • , Xiyan Li
    • , Jian Yang
    • , Tao Yu
    • , Ruohan Zhang
    • , Tianqing Zhang
    • , Deepak Saxena
    • , Michael Snyder
    • , Yingjie Wu
    •  & Xin Li
  • Article
    | Open Access

    The stem cells that maintain and repair adult joint tissues in mammals, including articular cartilage, remain incompletely defined. Here the authors perform lineage tracing studies in adult mice and find an ontogenetically defined progenitor cell population that is functional in the synovial joint and distinct from previously reported mesenchymal stem cell populations.

    • Anke J. Roelofs
    • , Janja Zupan
    • , Anna H. K. Riemen
    • , Karolina Kania
    • , Sharon Ansboro
    • , Nathan White
    • , Susan M. Clark
    •  & Cosimo De Bari
  • Article
    | Open Access

    Osteoarthritis (OA) is a debilitating and destructive joint disease for which disease modifying drugs are not available. Here the authors show that extracellular adenosine signalling via the A2AR receptor on chondrocytes is needed to prevent OA and that liposome-bound adenosine injection can treat the pathology in rats.

    • Carmen Corciulo
    • , Matin Lendhey
    • , Tuere Wilder
    • , Hanna Schoen
    • , Alexander Samuel Cornelissen
    • , Gregory Chang
    • , Oran D. Kennedy
    •  & Bruce N. Cronstein
  • Article
    | Open Access

    Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.

    • Gyda Bjornsdottir
    • , Stefania Benonisdottir
    • , Gardar Sveinbjornsson
    • , Unnur Styrkarsdottir
    • , Gudmar Thorleifsson
    • , G. Bragi Walters
    • , Aron Bjornsson
    • , Ingvar H. Olafsson
    • , Elfar Ulfarsson
    • , Arnor Vikingsson
    • , Ragnheidur Hansdottir
    • , Karl O. Karlsson
    • , Thorunn Rafnar
    • , Ingileif Jonsdottir
    • , Michael L. Frigge
    • , Augustine Kong
    • , Asmundur Oddsson
    • , Gisli Masson
    • , Olafur T. Magnusson
    • , Tomas Gudbjartsson
    • , Hreinn Stefansson
    • , Patrick Sulem
    • , Daniel Gudbjartsson
    • , Unnur Thorsteinsdottir
    • , Thorgeir E. Thorgeirsson
    •  & Kari Stefansson
  • Article
    | Open Access

    DEK is a secreted protein abundant in the synovia of patients with juvenile idiopathic arthritis. Here the authors show DEK is important for neutrophil extracellular trap formation and joint inflammation, and demonstrate therapeutic efficacy of DEK-targeting aptamers in a mouse model of arthritis.

    • Nirit Mor-Vaknin
    • , Anjan Saha
    • , Maureen Legendre
    • , Carmelo Carmona-Rivera
    • , M Asif Amin
    • , Bradley J. Rabquer
    • , Marta J. Gonzales-Hernandez
    • , Julie Jorns
    • , Smriti Mohan
    • , Srilakshmi Yalavarthi
    • , Dave A. Pai
    • , Kristine Angevine
    • , Shelley J. Almburg
    • , Jason S. Knight
    • , Barbara S. Adams
    • , Alisa E. Koch
    • , David A. Fox
    • , David R. Engelke
    • , Mariana J. Kaplan
    •  & David M. Markovitz
  • Article
    | Open Access

    Pten is known to regulate haematopoietic stem cell functions. Here the authors show that Ptenalteration of Notch signalling has stage-specific muscle regenerative functions in muscle stem cells by preventing premature differentiation of quiescent cells and enhancing the self-renewal of activated cells.

    • Feng Yue
    • , Pengpeng Bi
    • , Chao Wang
    • , Tizhong Shan
    • , Yaohui Nie
    • , Timothy L. Ratliff
    • , Timothy P. Gavin
    •  & Shihuan Kuang