Pathogenesis

  • Article
    | Open Access

    Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

    • David Michalovich
    • , Noelia Rodriguez-Perez
    • , Sylwia Smolinska
    • , Michal Pirozynski
    • , David Mayhew
    • , Sorif Uddin
    • , Stephanie Van Horn
    • , Milena Sokolowska
    • , Can Altunbulakli
    • , Andrzej Eljaszewicz
    • , Benoit Pugin
    • , Weronika Barcik
    • , Magdalena Kurnik-Lucka
    • , Ken A. Saunders
    • , Karen D. Simpson
    • , Peter Schmid-Grendelmeier
    • , Ruth Ferstl
    • , Remo Frei
    • , Noriane Sievi
    • , Malcolm Kohler
    • , Pawel Gajdanowicz
    • , Katrine B. Graversen
    • , Katrine Lindholm Bøgh
    • , Marek Jutel
    • , James R. Brown
    • , Cezmi A. Akdis
    • , Edith M. Hessel
    •  & Liam O’Mahony
  • Article
    | Open Access

    miRNA142-3p and Tet2 are separately known to regulate Treg. Here the authors show that miRNA142-3p targets Tet2 and by this opposes Treg differentiation in autoimmune diabetes.

    • Martin G. Scherm
    • , Isabelle Serr
    • , Adam M. Zahm
    • , Jonathan Schug
    • , Saverio Bellusci
    • , Rossella Manfredini
    • , Victoria K. Salb
    • , Katharina Gerlach
    • , Benno Weigmann
    • , Anette-Gabriele Ziegler
    • , Klaus H. Kaestner
    •  & Carolin Daniel
  • Article
    | Open Access

    The authors report a co-occurrence of the U2AF1 S34F splicing factor mutation and ROS1 translocations in lung adenocarcinomas and profile effects of S34F on transcriptome-wide RNA binding. They further show that U2AF1 S34F enhances invasive potential and alters splicing of ROS1 fusion transcripts

    • Mohammad S. Esfahani
    • , Luke J. Lee
    • , Young-Jun Jeon
    • , Ryan A. Flynn
    • , Henning Stehr
    • , Angela B. Hui
    • , Noriko Ishisoko
    • , Eric Kildebeck
    • , Aaron M. Newman
    • , Scott V. Bratman
    • , Matthew H. Porteus
    • , Howard Y. Chang
    • , Ash A. Alizadeh
    •  & Maximilian Diehn
  • Article
    | Open Access

    Innate immune cells can be trained by some stimuli or pathogen exposures to be metabolically and epigenetically altered such that they have different responses to subsequent exposures. Here the authors show that low-dose LPS trained macrophages and BCG-trained macrophages have opposing effects on fibrosis and inflammation in the context of systemic sclerosis.

    • Mohamed Jeljeli
    • , Luiza Gama Coelho Riccio
    • , Ludivine Doridot
    • , Charlotte Chêne
    • , Carole Nicco
    • , Sandrine Chouzenoux
    • , Quentin Deletang
    • , Yannick Allanore
    • , Niloufar Kavian
    •  & Frédéric Batteux
  • Article
    | Open Access

    Gut microbiota alterations, including enrichment of flagellated bacteria, are associated with metabolic syndrome and chronic inflammatory diseases. Here, Tran et al. show, in mice, that elicitation of mucosal anti-flagellin antibodies protects against experimental colitis and ameliorates diet-induced obesity.

    • Hao Q. Tran
    • , Ruth E. Ley
    • , Andrew T. Gewirtz
    •  & Benoit Chassaing
  • Article
    | Open Access

    The HLA-A*68:01 allele has been associated with severe influenza disease during the 2009 influenza pandemic. Here, the authors analyze influenza nucleoprotein specific HLA-A*68:01-restricted CD8+ T cells from human donors and show immunodominance of these cells in approximately 35% of HLA-A*68:01-expressing donors.

    • C. E. van de Sandt
    • , E. B. Clemens
    • , E. J. Grant
    • , L. C. Rowntree
    • , S. Sant
    • , H. Halim
    • , J. Crowe
    • , A. C. Cheng
    • , T. C. Kotsimbos
    • , M. Richards
    • , A. Miller
    • , S. Y. C. Tong
    • , J. Rossjohn
    • , T. H. O. Nguyen
    • , S. Gras
    • , W. Chen
    •  & K. Kedzierska
  • Article
    | Open Access

    Help from CD4+ T cells is important to induce CD8+ T cell memory responses, but mechanistic insights are lacking. Here, the authors show, by transcriptomics and epigenetics, how CD4+ T cells help program memory CD8+ T cells for help-independent recall by antigens, as well as for innate-like recall responses by IL-12/IL-18 and promoting survival by IL-15.

    • Tomasz Ahrends
    • , Julia Busselaar
    • , Tesa M. Severson
    • , Nikolina Bąbała
    • , Evert de Vries
    • , Astrid Bovens
    • , Lodewyk Wessels
    • , Fred van Leeuwen
    •  & Jannie Borst
  • Article
    | Open Access

    Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

    • Peter G. Boone
    • , Lauren K. Rochelle
    • , Joshua D. Ginzel
    • , Veronica Lubkov
    • , Wendy L. Roberts
    • , P. J. Nicholls
    • , Cheryl Bock
    • , Mei Lang Flowers
    • , Richard J. von Furstenberg
    • , Barry R. Stripp
    • , Pankaj Agarwal
    • , Alexander D. Borowsky
    • , Robert D. Cardiff
    • , Larry S. Barak
    • , Marc G. Caron
    • , H. Kim Lyerly
    •  & Joshua C. Snyder
  • Article
    | Open Access

    Tissue context can dictate why a gene can have seemingly opposing functions in different settings. ELF3 is tumor suppressive in many cancers of epithelial origin but in lung cancer, the authors describe an oncogenic role in the adenocarcinoma histology of non-small cell lung cancer.

    • Katey S. S. Enfield
    • , Erin A. Marshall
    • , Christine Anderson
    • , Kevin W. Ng
    • , Sara Rahmati
    • , Zhaolin Xu
    • , Megan Fuller
    • , Katy Milne
    • , Daniel Lu
    • , Rocky Shi
    • , David A. Rowbotham
    • , Daiana D. Becker-Santos
    • , Fraser D. Johnson
    • , John C. English
    • , Calum E. MacAulay
    • , Stephen Lam
    • , William W. Lockwood
    • , Raj Chari
    • , Aly Karsan
    • , Igor Jurisica
    •  & Wan L. Lam
  • Article
    | Open Access

    Here, the authors identify a broadly neutralizing antibody from an HIV-infected person that recognizes the membrane-proximal external region (MPER) of HIV envelope glycoprotein (Env) and has a short CDRH3 and low polyreactivity. Structural analysis shows how the antibody binds the MPER and Env on the viral membrane.

    • Lei Zhang
    • , Adriana Irimia
    • , Lingling He
    • , Elise Landais
    • , Kimmo Rantalainen
    • , Daniel P. Leaman
    • , Thomas Vollbrecht
    • , Armando Stano
    • , Daniel I. Sands
    • , Arthur S. Kim
    • , George Miiro
    • , Jennifer Serwanga
    • , Anton Pozniak
    • , Dale McPhee
    • , Oliver Manigart
    • , Lawrence Mwananyanda
    • , Etienne Karita
    • , André Inwoley
    • , Walter Jaoko
    • , Jack DeHovitz
    • , Linda-Gail Bekker
    • , Punnee Pitisuttithum
    • , Robert Paris
    • , Susan Allen
    • , Pascal Poignard
    • , Dennis R. Burton
    • , Ben Murrell
    • , Andrew B. Ward
    • , Jiang Zhu
    • , Ian A. Wilson
    •  & Michael B. Zwick
  • Article
    | Open Access

    There is disproportionally high cancer prevalence in males. Here, the authors analyse the tumour suppressor p53 in sporadic cancers, highlighting a higher incidence of its mutation in males. Males are further disadvantaged by a failure to shield against the expression of damaged X-linked genes in p53-networks. These factors likely contribute to sex-disparity.

    • Sue Haupt
    • , Franco Caramia
    • , Alan Herschtal
    • , Thierry Soussi
    • , Guillermina Lozano
    • , Hu Chen
    • , Han Liang
    • , Terence P. Speed
    •  & Ygal Haupt
  • Article
    | Open Access

    ISG15 is a ubiquitin-like modifier that can be upregulated in response to bacterial infections. Here, the authors use proteomics to identify endogenous ISGylation substrates in the liver of Listeria monocytogenes infected mice and show that ISGylation alters basal and infection-induced autophagy.

    • Yifeng Zhang
    • , Fabien Thery
    • , Nicholas C. Wu
    • , Emma K. Luhmann
    • , Olivier Dussurget
    • , Mariko Foecke
    • , Clara Bredow
    • , Daniel Jiménez-Fernández
    • , Kevin Leandro
    • , Antje Beling
    • , Klaus-Peter Knobeloch
    • , Francis Impens
    • , Pascale Cossart
    •  & Lilliana Radoshevich
  • Article
    | Open Access

    The regenerating islet-derived (REG) protein family suppresses cell death and promotes cell proliferation. Here the authors report that the lncRNA REG1CP forms an RNA–DNA triplex at the promoter of REG3A gene to increase its expression.

    • Hamed Yari
    • , Lei Jin
    • , Liu Teng
    • , Yufang Wang
    • , Yongyan Wu
    • , Guang Zhi Liu
    • , Wei Gao
    • , Jin Liang
    • , Yanfeng Xi
    • , Yu Chen Feng
    • , Chunming Zhang
    • , Yuan Yuan Zhang
    • , Hessam Tabatabaee
    • , Ting La
    • , Rui Hong Yang
    • , Fu Hua Wang
    • , Xu Guang Yan
    • , Margaret Farrelly
    • , Rodney Scott
    • , Tao Liu
    • , Rick F. Thorne
    • , Su Tang Guo
    •  & Xu Dong Zhang
  • Article
    | Open Access

    Brain damage induces systemic inflammation, but insights and implication of this induction is still unclear. Here the authors show, using rat and mouse focal cerebral ischemia models, that the damaged brain signals via the VEGF-C/VEFGR3 axis to activate inflammatory responses in the draining cervical lymph nodes to induce systemic inflammation.

    • Elga Esposito
    • , Bum Ju Ahn
    • , Jingfei Shi
    • , Yoshihiko Nakamura
    • , Ji Hyun Park
    • , Emiri T. Mandeville
    • , Zhanyang Yu
    • , Su Jing Chan
    • , Rakhi Desai
    • , Ayumi Hayakawa
    • , Xunming Ji
    • , Eng H. Lo
    •  & Kazuhide Hayakawa
  • Article
    | Open Access

    NLRP3 activation by Leishmania parasites is critical to the outcome of the disease. Here the authors show that LRV, a virus infecting Leishmania strains associated with more severe human disease, enables the parasite to suppress the inflammasome by activating type 1 interferon through TLR3, which leads to autophagy-mediated NLRP3 degradation.

    • Renan V. H. de Carvalho
    • , Djalma S. Lima-Junior
    • , Marcus Vinícius G. da Silva
    • , Marisa Dilucca
    • , Tamara S. Rodrigues
    • , Catarina V. Horta
    • , Alexandre L. N. Silva
    • , Patrick F. da Silva
    • , Fabiani G. Frantz
    • , Lucas B. Lorenzon
    • , Marcos Michel Souza
    • , Fausto Almeida
    • , Lilian M. Cantanhêde
    • , Ricardo de Godoi M. Ferreira
    • , Angela K. Cruz
    •  & Dario S. Zamboni
  • Article
    | Open Access

    T cells from narcolepsy patients were recently reported to recognize hypocretin, a wakefulness-promoting neurohormone, suggesting autoimmune origin of the disease. Here the authors show that hypocretin-specific T cells expand both in healthy controls and in narcolepsy patients, and identify preliminary features that may distinguish them.

    • Wei Jiang
    • , James R. Birtley
    • , Shu-Chen Hung
    • , Weiqi Wang
    • , Shin-Heng Chiou
    • , Claudia Macaubas
    • , Birgitte Kornum
    • , Lu Tian
    • , Huang Huang
    • , Lital Adler
    • , Grant Weaver
    • , Liying Lu
    • , Alexandra Ilstad-Minnihan
    • , Sriram Somasundaram
    • , Sashi Ayyangar
    • , Mark M. Davis
    • , Lawrence J. Stern
    •  & Elizabeth D. Mellins
  • Article
    | Open Access

    Redirection of the TCA cycle intermediate aconitate to itaconate production has anti-inflammatory effects. Here the authors show that the itaconate derivative 4-octyl-itaconate is anti-inflammatory partly as a result of inhibiting GAPDH enzymatic activity and thereby glycolysis in macrophages.

    • Shan-Ting Liao
    • , Chao Han
    • , Ding-Qiao Xu
    • , Xiao-Wei Fu
    • , Jun-Song Wang
    •  & Ling-Yi Kong
  • Article
    | Open Access

    TP53 mutations can cause increased risk for cancers. Here, the authors show a noncoding polymorphism in TP53 increases risk of some cancers but delays onset of others, and in a mouse model show this is via alteration of microRNA targeting sites that differ in impact depending on the tissue.

    • Qipan Deng
    • , Hui Hu
    • , Xinfang Yu
    • , Shuanglin Liu
    • , Lei Wang
    • , Weiqun Chen
    • , Chi Zhang
    • , Zhaoyang Zeng
    • , Ya Cao
    • , Zijun Y. Xu-Monette
    • , Ling Li
    • , Mingzhi Zhang
    • , Steven Rosenfeld
    • , Shideng Bao
    • , Eric Hsi
    • , Ken H. Young
    • , Zhongxin Lu
    •  & Yong Li
  • Article
    | Open Access

    T cell bystander activation is induced by systemic inflammation. Here the authors show, using mouse model systems and correlating with human vaccination data, that localized inflammation elicits bystander activation, and that CXCR3 specifically recruits memory CD8+ T cells to sites of activated antigen-presenting cells for bystander activation.

    • Nicholas J. Maurice
    • , M. Juliana McElrath
    • , Erica Andersen-Nissen
    • , Nicole Frahm
    •  & Martin Prlic
  • Article
    | Open Access

    Familial cortical myoclonic tremor (FAME) has so far been mapped to regions on chromosome 2, 3, 5 and 8 and pentameric repeat expansions in SAMD12 were identified as cause of FAME1. Here, Corbett et al. identify ATTTT/ATTTC repeat expansions in intron 1 of STARD7 in individuals with FAME2.”

    • Mark A. Corbett
    • , Thessa Kroes
    • , Liana Veneziano
    • , Mark F. Bennett
    • , Rahel Florian
    • , Amy L. Schneider
    • , Antonietta Coppola
    • , Laura Licchetta
    • , Silvana Franceschetti
    • , Antonio Suppa
    • , Aaron Wenger
    • , Davide Mei
    • , Manuela Pendziwiat
    • , Sabine Kaya
    • , Massimo Delledonne
    • , Rachel Straussberg
    • , Luciano Xumerle
    • , Brigid Regan
    • , Douglas Crompton
    • , Anne-Fleur van Rootselaar
    • , Anthony Correll
    • , Rachael Catford
    • , Francesca Bisulli
    • , Shreyasee Chakraborty
    • , Sara Baldassari
    • , Paolo Tinuper
    • , Kirston Barton
    • , Shaun Carswell
    • , Martin Smith
    • , Alfredo Berardelli
    • , Renee Carroll
    • , Alison Gardner
    • , Kathryn L. Friend
    • , Ilan Blatt
    • , Michele Iacomino
    • , Carlo Di Bonaventura
    • , Salvatore Striano
    • , Julien Buratti
    • , Boris Keren
    • , Caroline Nava
    • , Sylvie Forlani
    • , Gabrielle Rudolf
    • , Edouard Hirsch
    • , Eric Leguern
    • , Pierre Labauge
    • , Simona Balestrini
    • , Josemir W. Sander
    • , Zaid Afawi
    • , Ingo Helbig
    • , Hiroyuki Ishiura
    • , Shoji Tsuji
    • , Sanjay M. Sisodiya
    • , Giorgio Casari
    • , Lynette G. Sadleir
    • , Riaan van Coller
    • , Marina A. J. Tijssen
    • , Karl Martin Klein
    • , Arn M. J. M. van den Maagdenberg
    • , Federico Zara
    • , Renzo Guerrini
    • , Samuel F. Berkovic
    • , Tommaso Pippucci
    • , Laura Canafoglia
    • , Melanie Bahlo
    • , Pasquale Striano
    • , Ingrid E. Scheffer
    • , Francesco Brancati
    • , Christel Depienne
    •  & Jozef Gecz
  • Article
    | Open Access

    Interval cancer patients are more likely to carry rare gene mutations than screen-detected breast cancer patients. Here, the authors report that interval cancer patients are more likely cancer survivors and are at a greater risk of developing other non-breast tumors.

    • Felix Grassmann
    • , Wei He
    • , Mikael Eriksson
    • , Marike Gabrielson
    • , Per Hall
    •  & Kamila Czene
  • Article
    | Open Access

    Roquin-1 is a posttranscriptional regulator that controls the expression of many immune-related genes such as ICOS and TNFA. Here, the authors report a homozygous R688* loss of function mutation in Roquin-1 in a patient with syndromic uncontrolled hyperinflammation associated with immune cell activation and hypercytokinemia.

    • S. J. Tavernier
    • , V. Athanasopoulos
    • , P. Verloo
    • , G. Behrens
    • , J. Staal
    • , D. J. Bogaert
    • , L. Naesens
    • , M. De Bruyne
    • , S. Van Gassen
    • , E. Parthoens
    • , J. Ellyard
    • , J. Cappello
    • , L. X. Morris
    • , H. Van Gorp
    • , G. Van Isterdael
    • , Y. Saeys
    • , M. Lamkanfi
    • , P. Schelstraete
    • , J. Dehoorne
    • , V. Bordon
    • , R. Van Coster
    • , B. N. Lambrecht
    • , B. Menten
    • , R. Beyaert
    • , C. G. Vinuesa
    • , V. Heissmeyer
    • , M. Dullaers
    •  & F. Haerynck
  • Article
    | Open Access

    B-1a B cells are innate-like cells with biased reactivity to bacteria and self-antigens. Here the authors show that reduced interleukin-7 in developing fetal liver-derived pro-B cells induces premature immunoglobulin κ rearrangement, alleviating the requirement for a pre-BCR selection stage and allowing the generation of autoreactive B1-a B cells.

    • Jason B. Wong
    • , Susannah L. Hewitt
    • , Lynn M. Heltemes-Harris
    • , Malay Mandal
    • , Kristen Johnson
    • , Klaus Rajewsky
    • , Sergei B. Koralov
    • , Marcus R. Clark
    • , Michael A. Farrar
    •  & Jane A. Skok
  • Article
    | Open Access

    Down syndrome (DS) is caused by trisomy 21 (T21), but the underlying etiology of the related immune and neurological dysfunction is unclear. Here, the authors show that T21 activates the kynurenine pathway via increased interferon receptor copy number, which could contribute to DS pathophysiology.

    • Rani K. Powers
    • , Rachel Culp-Hill
    • , Michael P. Ludwig
    • , Keith P. Smith
    • , Katherine A. Waugh
    • , Ross Minter
    • , Kathryn D. Tuttle
    • , Hannah C. Lewis
    • , Angela L. Rachubinski
    • , Ross E. Granrath
    • , María Carmona-Iragui
    • , Rebecca B. Wilkerson
    • , Darcy E. Kahn
    • , Molishree Joshi
    • , Alberto Lleó
    • , Rafael Blesa
    • , Juan Fortea
    • , Angelo D’Alessandro
    • , James C. Costello
    • , Kelly D. Sullivan
    •  & Joaquin M. Espinosa
  • Article
    | Open Access

    Mosaic loss of chromosome Y (mLOY) is associated with age and smoking but also genetic factors play a role. Here, Terao et al. perform GWAS for mLOY in 95,380 Japanese men and identify 46 loci that overlap with hematopoietic stem cell enhancers and transcription factor binding sites critical for hematopoiesis.

    • Chikashi Terao
    • , Yukihide Momozawa
    • , Kazuyoshi Ishigaki
    • , Eiryo Kawakami
    • , Masato Akiyama
    • , Po-Ru Loh
    • , Giulio Genovese
    • , Hiroki Sugishita
    • , Tazro Ohta
    • , Makoto Hirata
    • , John R. B. Perry
    • , Koichi Matsuda
    • , Yoshinori Murakami
    • , Michiaki Kubo
    •  & Yoichiro Kamatani
  • Article
    | Open Access

    CYLD cutaneous syndrome (also known as Brooke-Spiegler syndrome) is characterised by germline mutations in the tumor suppressor CYLD. Here, the authors highlight recurrent mutations in DNMT3A and BCOR, indicating a role for epigenetic dysregulation in this rare genetic skin disease.

    • Helen R. Davies
    • , Kirsty Hodgson
    • , Edward Schwalbe
    • , Jonathan Coxhead
    • , Naomi Sinclair
    • , Xueqing Zou
    • , Simon Cockell
    • , Akhtar Husain
    • , Serena Nik-Zainal
    •  & Neil Rajan
  • Article
    | Open Access

    The master transcription factor RORγt, encoded by the RORC gene, controls the polarization of CD4+ T cells expressing interleukin-17 (Th17). Here the authors describe several regulatory elements at the RORC locus that are recognized by NFAT and NFkB to induce a permissive epigenetic configuration of the RORC gene for RORγt expression and Th17 differentiation.

    • Hanane Yahia-Cherbal
    • , Magda Rybczynska
    • , Domenica Lovecchio
    • , Tharshana Stephen
    • , Chloé Lescale
    • , Katarzyna Placek
    • , Jérome Larghero
    • , Lars Rogge
    •  & Elisabetta Bianchi
  • Article
    | Open Access

    The Chlamydia pneumoniae adhesin LIPP plays a role in host cell entry and infection. Here, the authors find that LIPP binds to the host plasma membrane and mediates phosphatidylserine translocation, enhancing pathogen internalization without induction of apoptosis.

    • Jan N. Galle
    • , Tim Fechtner
    • , Thorsten Eierhoff
    • , Winfried Römer
    •  & Johannes H. Hegemann
  • Article
    | Open Access

    Human cytomegalovirus (HCMV) has evolved several mechanisms to evade the host immune response. Here, Park et al. show that HCMV-encoded US7 and US8 proteins bind TLR3 and TLR4 and facilitate TLR degradation by distinct mechanisms, including ER-associated and lysosomal degradation.

    • Areum Park
    • , Eun A. Ra
    • , Taeyun A. Lee
    • , Hyun jin Choi
    • , Eunhye Lee
    • , Sujin Kang
    • , Jun-Young Seo
    • , Sungwook Lee
    •  & Boyoun Park
  • Article
    | Open Access

    Cytosolic mitochondrial DNA (mtDNA) plays a role in innate antiviral immunity but how this is triggered during infection remains unclear. Here, the authors provide evidence that the Influenza virus protein M2 stimulates translocation of mtDNA into the cytosol in a MAVS-dependent manner.

    • Miyu Moriyama
    • , Takumi Koshiba
    •  & Takeshi Ichinohe
  • Article
    | Open Access

    Many human antibodies that neutralize Zika virus recognize quaternary epitopes on the envelope (E) protein. Here, Metz et al. engineer stable recombinant homodimers of Zika virus E protein and show that it induces neutralizing antibodies in mice that recognize similar epitopes as human antibodies from Zika infected people.

    • Stefan W. Metz
    • , Ashlie Thomas
    • , Alex Brackbill
    • , John Forsberg
    • , Michael J. Miley
    • , Cesar A. Lopez
    • , Helen M. Lazear
    • , Shaomin Tian
    •  & Aravinda M. de Silva
  • Article
    | Open Access

    Trophoblasts play a critical role in maintaining immunological tolerance at maternal–fetal interface. Here the authors show that IL-35 is made by trophoblasts, converts T cells to immune tolerant iTR35 cells, and is critical to prevent spontaneous abortion.

    • Jia Liu
    • , Shengnan Hao
    • , Xi Chen
    • , Hui Zhao
    • , Lutao Du
    • , Hanxiao Ren
    • , Chuanxin Wang
    •  & Haiting Mao
  • 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

    High-throughput assays for TCR specificity are a bottleneck in understanding T cell immunity and harnessing it for medicine. Here the authors develop a functional screening method to identify T cell specificity in the natural context of peptide-MHC presentation, enabling detection of physiologically relevant T cell antigens from large libraries of peptide-coding sequences.

    • Govinda Sharma
    • , Craig M. Rive
    •  & Robert A. Holt
  • Article
    | Open Access

    Vectors used in gene therapy for hemoglobin disorders carry globin in a reverse-orientation to prevent the loss of key regulatory elements by RNA splicing, but this limits their efficiency. Here, the authors develop a vector carrying β-globin in a forward orientation and show that it has improved titers and transduction efficiency in humanized mice and nonhuman primates.

    • Naoya Uchida
    • , Matthew M. Hsieh
    • , Lydia Raines
    • , Juan J. Haro-Mora
    • , Selami Demirci
    • , Aylin C. Bonifacino
    • , Allen E. Krouse
    • , Mark E. Metzger
    • , Robert E. Donahue
    •  & John F. Tisdale
  • Article
    | Open Access

    In-depth characterization of adeno-associated virus (AAV)-mediated CRISPR delivery is still lacking. Here, the authors show high levels of integration into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in vivo.

    • Killian S. Hanlon
    • , Benjamin P. Kleinstiver
    • , Sara P. Garcia
    • , Mikołaj P. Zaborowski
    • , Adrienn Volak
    • , Stefan E. Spirig
    • , Alissa Muller
    • , Alexander A. Sousa
    • , Shengdar Q. Tsai
    • , Niclas E. Bengtsson
    • , Camilla Lööv
    • , Martin Ingelsson
    • , Jeffrey S. Chamberlain
    • , David P. Corey
    • , Martin J. Aryee
    • , J. Keith Joung
    • , Xandra O. Breakefield
    • , Casey A. Maguire
    •  & Bence György
  • Article
    | Open Access

    How antibody reaches tissues from circulation is critical for understanding antibody-mediated immunity. Here the authors show that IgG extravasation in the skin is mediated by endothelial caveolin transport independently of FcR, and is targetable by imatinib, which reduces IgG-dependent pathology in a mouse model of pemphigus.

    • Sachiko Ono
    • , Gyohei Egawa
    • , Takashi Nomura
    • , Akihiko Kitoh
    • , Teruki Dainichi
    • , Atsushi Otsuka
    • , Saeko Nakajima
    • , Masayuki Amagai
    • , Fumi Matsumoto
    • , Mami Yamamoto
    • , Yoshiaki Kubota
    • , Toshiyuki Takai
    • , Tetsuya Honda
    •  & Kenji Kabashima
  • Article
    | Open Access

    One aspect of ageing on immunity is attributed to accelerated thymic atrophy, but the underlying mechanism is still lacking. Here the authors show, using conditional reporter mouse models, that both atrophy and regeneration of the thymus are regulated by rate-limiting morphological changes in epithelial stroma, independent of cell death or proliferation.

    • Thomas Venables
    • , Ann V. Griffith
    • , Alice DeAraujo
    •  & Howard T. Petrie
  • Article
    | Open Access

    Conserved regions of the antibody molecule impact its downstream biological effects. Here the authors show that a rigid hinge conformation increases the agonistic activity of CD40 and DR5 antibodies, distinctly from FcγR-binding, suggesting that the hinge and FcR binding regions can be separately modified to optimize therapies.

    • Xiaobo Liu
    • , Yingjie Zhao
    • , Huan Shi
    • , Yan Zhang
    • , Xueying Yin
    • , Mingdong Liu
    • , Huihui Zhang
    • , Yongning He
    • , Boxun Lu
    • , Tengchuan Jin
    •  & Fubin Li
  • Article
    | Open Access

    B cell response and antibody production are generally facilitated by CD4+ follicular helper (Tfh) cells. Here the authors identify a subset of CXCR5+PD1+CD8+ Tfh cells that is normally suppressed by STAT5 signaling, so that STAT5 deficiency in mice increases the number of these CD8+ Tfh cells and induces concomitant production of autoantibodies.

    • Yuhong Chen
    • , Mei Yu
    • , Yongwei Zheng
    • , Guoping Fu
    • , Gang Xin
    • , Wen Zhu
    • , Lan Luo
    • , Robert Burns
    • , Quan-Zhen Li
    • , Alexander L. Dent
    • , Nan Zhu
    • , Weiguo Cui
    • , Laurent Malherbe
    • , Renren Wen
    •  & Demin Wang
  • Article
    | Open Access

    Immunotherapy can induce antigen spreading of antitumor T cell response, which correlates with better outcomes. Here the authors show that tissue-resident memory CD8 T cells promote antigen spreading via lysing tumor cells and promoting their uptake and cross-presentation by dendritic cells, thereby eliciting de novo T cell responses.

    • Evelyn Menares
    • , Felipe Gálvez-Cancino
    • , Pablo Cáceres-Morgado
    • , Ehsan Ghorani
    • , Ernesto López
    • , Ximena Díaz
    • , Juan Saavedra-Almarza
    • , Diego A. Figueroa
    • , Eduardo Roa
    • , Sergio A. Quezada
    •  & Alvaro Lladser
  • Article
    | Open Access

    TFF3 secretion by goblet cells regulates mucus viscosity and wound healing, but a receptor for TFF3 has not been identified. Here, the authors show that TFF3 binds LINGO2 to de-repress and enhance EGFR signaling that drives wound healing and immunity against helminths.

    • Nicole Maloney Belle
    • , Yingbiao Ji
    • , Karl Herbine
    • , Yun Wei
    • , JoonHyung Park
    • , Kelly Zullo
    • , Li-Yin Hung
    • , Sriram Srivatsa
    • , Tanner Young
    • , Taylor Oniskey
    • , Christopher Pastore
    • , Wildaliz Nieves
    • , Ma Somsouk
    •  & De’Broski R. Herbert
  • Article
    | Open Access

    Causally linking a mutation to clinical phenotypes in rare hereditary diseases is both challenging and illuminating. Here the authors identify PI3Kɣ mutations in a patient with immune dysregulation, and recapitulate the phenotypes in PI3Kɣ-deficient mice by exposing them to natural microbiota from pet-shop mice.

    • Andrew J. Takeda
    • , Timothy J. Maher
    • , Yu Zhang
    • , Stephen M. Lanahan
    • , Molly L. Bucklin
    • , Susan R. Compton
    • , Paul M. Tyler
    • , William A. Comrie
    • , Makoto Matsuda
    • , Kenneth N. Olivier
    • , Stefania Pittaluga
    • , Joshua J. McElwee
    • , Debra A. Long Priel
    • , Douglas B. Kuhns
    • , Roger L. Williams
    • , Peter J. Mustillo
    • , Matthias P. Wymann
    • , V. Koneti Rao
    •  & Carrie L. Lucas
  • Article
    | Open Access

    Here, Khan et al. show that enhanced Zika virus replication in the lower female reproductive tract of mice and macaques associates with low expression of RNA sensing pattern recognition receptors, while IFNAR signaling may be critical in preventing viral dissemination to distal tissues.

    • Shahzada Khan
    • , Irene Lew
    • , Frank Wu
    • , Linda Fritts
    • , Krystal A. Fontaine
    • , Sakshi Tomar
    • , Martin Trapecar
    • , Hesham M. Shehata
    • , Melanie Ott
    • , Christopher J. Miller
    •  & Shomyseh Sanjabi
  • Article
    | Open Access

    Pfs25 is a transmission-blocking vaccine candidate for Plasmodium. Here, McLeod et al. analyze the antibody response to Pfs25 in sera from a clinical trial evaluating a Pfs25 vaccine candidate, identify a potent transmission-blocking antibody and determine recognized epitopes on Pfs25.

    • Brandon McLeod
    • , Kazutoyo Miura
    • , Stephen W. Scally
    • , Alexandre Bosch
    • , Ngan Nguyen
    • , Hanjun Shin
    • , Dongkyoon Kim
    • , Wayne Volkmuth
    • , Sebastian Rämisch
    • , Jessica A. Chichester
    • , Stephen Streatfield
    • , Colleen Woods
    • , William R. Schief
    • , Daniel Emerling
    • , C. Richter King
    •  & Jean-Philippe Julien
  • Article
    | Open Access

    Here, the authors show that the time elapsed between Zika infection and subsequent dengue virus infection affects the magnitude and durability of the antibody and cell-mediated immune responses against dengue virus, but not viremia. This research in non-human primates has implications for co-endemic regions and vaccination.

    • Erick X. Pérez-Guzmán
    • , Petraleigh Pantoja
    • , Crisanta Serrano-Collazo
    • , Mariah A. Hassert
    • , Alexandra Ortiz-Rosa
    • , Idia V. Rodríguez
    • , Luis Giavedoni
    • , Vida Hodara
    • , Laura Parodi
    • , Lorna Cruz
    • , Teresa Arana
    • , Laura J. White
    • , Melween I. Martínez
    • , Daniela Weiskopf
    • , James D. Brien
    • , Aravinda de Silva
    • , Amelia K. Pinto
    •  & Carlos A. Sariol
  • Article
    | Open Access

    Nanoparticles are a promising approach to increase immunogenicity of protein antigens for vaccines. Here, Brouwer et al. design self-assembling, two-component protein NPs that present native-like SOSIP trimers of HIV envelope protein and determine immunogenicity in a small animal model.

    • Philip J. M. Brouwer
    • , Aleksandar Antanasijevic
    • , Zachary Berndsen
    • , Anila Yasmeen
    • , Brooke Fiala
    • , Tom P. L. Bijl
    • , Ilja Bontjer
    • , Jacob B. Bale
    • , William Sheffler
    • , Joel D. Allen
    • , Anna Schorcht
    • , Judith A. Burger
    • , Miguel Camacho
    • , Daniel Ellis
    • , Christopher A. Cottrell
    • , Anna-Janina Behrens
    • , Marco Catalano
    • , Iván del Moral-Sánchez
    • , Thomas J. Ketas
    • , Celia LaBranche
    • , Marit J. van Gils
    • , Kwinten Sliepen
    • , Lance J. Stewart
    • , Max Crispin
    • , David C. Montefiori
    • , David Baker
    • , John P. Moore
    • , Per Johan Klasse
    • , Andrew B. Ward
    • , Neil P. King
    •  & Rogier W. Sanders
  • Article
    | Open Access

    Allergic asthma symptoms may be controlled, but currently no effective therapy exist to address the underlying pathology. Here the authors show, using mouse model of adoptive cell transfer, that CD4-CD8- T cells can suppress the function of dendritic cells and T follicular helper cells via Lag3 to provide allergen-specific protection from asthma.

    • Dan Tian
    • , Lu Yang
    • , Song Wang
    • , Yanbing Zhu
    • , Wen Shi
    • , Chunpan Zhang
    • , Hua Jin
    • , Yue Tian
    • , Hufeng Xu
    • , Guangyong Sun
    • , Kai Liu
    • , Zhongtao Zhang
    •  & Dong Zhang