Anatomy

  • Article
    | Open Access

    The kidney is vascularized with highly specialized and zonated endothelial cells that are essential for its filtration function. Here, Barry et al. provide a single-cell RNA sequencing analysis of the kidney vasculature that highlights its transcriptional heterogeneity and uncovers pathways important for its development and function.

    • David M. Barry
    • , Elizabeth A. McMillan
    • , Balvir Kunar
    • , Raphael Lis
    • , Tuo Zhang
    • , Tyler Lu
    • , Edward Daniel
    • , Masataka Yokoyama
    • , Jesus M. Gomez-Salinero
    • , Angara Sureshbabu
    • , Ondine Cleaver
    • , Annarita Di Lorenzo
    • , Mary E. Choi
    • , Jenny Xiang
    • , David Redmond
    • , Sina Y. Rabbany
    • , Thangamani Muthukumar
    •  & Shahin Rafii
  • Article
    | Open Access

    Sensory stimuli usually arrive simultaneously but the neural-circuit mechanisms that combine multiple streams of sensory information are incompletely understood. The authors here show that visual-auditory pairing drives plasticity in multi-modal neuron networks within the mouse visual cortex.

    • Thomas Knöpfel
    • , Yann Sweeney
    • , Carola I. Radulescu
    • , Nawal Zabouri
    • , Nazanin Doostdar
    • , Claudia Clopath
    •  & Samuel J. Barnes
  • 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

    Attention is known to enhance relevant information in our environment, yet its underlying neural computations remain unclear. Here, the authors provide evidence that the degree to which a neural population can normalize itself results in greater potential for attentional benefits.

    • Ilona M. Bloem
    •  & Sam Ling
  • Article
    | Open Access

    Spinal pain is a major clinical problem. Here the authors show that osteoclasts create porous area of endplates of the vertebrae and sensory innervation of porous endplates by Netrin-1 release from osteoclasts mediates PGE2-induced spinal hypersensitivity in mice.

    • Shuangfei Ni
    • , Zemin Ling
    • , Xiao Wang
    • , Yong Cao
    • , Tianding Wu
    • , Ruoxian Deng
    • , Janet L. Crane
    • , Richard Skolask
    • , Shadpour Demehril
    • , Gehua Zhen
    • , Amit Jain
    • , Panfeng Wu
    • , Dayu Pan
    • , Bo Hu
    • , Xiao Lyu
    • , Yusheng Li
    • , Hao Chen
    • , Huabin Qi
    • , Yun Guan
    • , Xinzhong Dong
    • , Mei Wan
    • , Xuenong Zou
    • , Hongbin Lu
    • , Jianzhong Hu
    •  & Xu Cao
  • 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

    The visual word form area (VWFA) is a brain region associated with written language, but it has also been linked to visuospatial attention. Here, the authors reveal distinct structural and functional circuits linking VWFA with language and attention networks, and demonstrate that these circuits separately predict language and attention abilities.

    • Lang Chen
    • , Demian Wassermann
    • , Daniel A. Abrams
    • , John Kochalka
    • , Guillermo Gallardo-Diez
    •  & Vinod Menon
  • Article
    | Open Access

    Olfactory bulb neurogenesis raises the question of how persistent olfactory memories are retained while remaining flexible to encode new memories. Here, the authors show that new neurons can only support a single odor memory within their critical period of integration into the circuit.

    • Jérémy Forest
    • , Mélissa Moreno
    • , Matthias Cavelius
    • , Laura Chalençon
    • , Anne Ziessel
    • , Joëlle Sacquet
    • , Marion Richard
    • , Anne Didier
    •  & Nathalie Mandairon
  • 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

    How reproducible human kidney organoids derived from different iPSC lines are, and how faithful they are to human kidney tissue remain unclear. Here, the authors use four human iPSC lines to derive kidney organoids and show how organoid composition is reproducible, comparable to human tissue and of improved quality after transplantation.

    • Ayshwarya Subramanian
    • , Eriene-Heidi Sidhom
    • , Maheswarareddy Emani
    • , Katherine Vernon
    • , Nareh Sahakian
    • , Yiming Zhou
    • , Maria Kost-Alimova
    • , Michal Slyper
    • , Julia Waldman
    • , Danielle Dionne
    • , Lan T. Nguyen
    • , Astrid Weins
    • , Jamie L. Marshall
    • , Orit Rosenblatt-Rosen
    • , Aviv Regev
    •  & Anna Greka
  • Article
    | Open Access

    Zebrafish larvae can binocularly detect prey objects in order to strike but lack ipsilateral retinotectal fibers for binocular superposition of visual information. Here the authors describe commissural intertectal neurons and show that they are required for the initiation of capture strikes.

    • Christoph Gebhardt
    • , Thomas O. Auer
    • , Pedro M. Henriques
    • , Gokul Rajan
    • , Karine Duroure
    • , Isaac H. Bianco
    •  & Filippo Del Bene
  • Article
    | Open Access

    Cytotoxic T lymphocytes (CTLs) eliminate virus-infected and cancerous cells by secreting the pore-forming protein (perforin) and pro-apoptotic serine proteases (granzymes). Here authors show that two mechanisms protect the membranes of CTLs from disruption by perforin and granzymes.

    • Jesse A. Rudd-Schmidt
    • , Adrian W. Hodel
    • , Tahereh Noori
    • , Jamie A. Lopez
    • , Hyun-Jung Cho
    • , Sandra Verschoor
    • , Annette Ciccone
    • , Joseph A. Trapani
    • , Bart W. Hoogenboom
    •  & Ilia Voskoboinik
  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    • , Camilla M. Reehorst
    • , Rebecca Nightingale
    • , Irvin Ng
    • , Holly Anderton
    • , Sheren Al-Obaidi
    • , Analia Lesmana
    • , Cameron M. Scott
    • , Paul Ioannidis
    • , Hina Kalra
    • , Shivakumar Keerthikumar
    • , Lars Tögel
    • , Angela Rigopoulos
    • , Sylvia J. Gong
    • , David S. Williams
    • , Prusoth Yoganantharaja
    • , Kim Bell-Anderson
    • , Suresh Mathivanan
    • , Yann Gibert
    • , Scott Hiebert
    • , Andrew M. Scott
    • , Matthew J. Watt
    •  & John M. Mariadason
  • 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

    In congenitally blind people, tactile stimuli can activate the occipital (visual) cortex. Here, the authors show using magnetoencephalography (MEG) that occipital activation can occur within 35 ms following tactile stimulation, suggesting the existence of a fast thalamocortical pathway for touch in congenitally blind humans.

    • Franziska Müller
    • , Guiomar Niso
    • , Soheila Samiee
    • , Maurice Ptito
    • , Sylvain Baillet
    •  & Ron Kupers
  • 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

    During high-intensity exercise, muscles convert glucose to lactate, in a process that is energetically less efficient than respiration. Here the authors develop a computational model based on muscle proteomic data showing that bypassing mitochondrial complex I increases ATP production rates, and validate these model predictions in an exercise test on 5 subjects.

    • Avlant Nilsson
    • , Elias Björnson
    • , Mikael Flockhart
    • , Filip J. Larsen
    •  & Jens Nielsen
  • 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

    Pu-erh tea displays cholesterol-lowering properties. Here, Huang et al. show that this is mostly due to the action of a pigment in Pu-erh tea that induces changes in certain gut microbiota and bile acid levels, thus modulating the gut-liver metabolic axis.

    • Fengjie Huang
    • , Xiaojiao Zheng
    • , Xiaohui Ma
    • , Runqiu Jiang
    • , Wangyi Zhou
    • , Shuiping Zhou
    • , Yunjing Zhang
    • , Sha Lei
    • , Shouli Wang
    • , Junliang Kuang
    • , Xiaolong Han
    • , Meilin Wei
    • , Yijun You
    • , Mengci Li
    • , Yitao Li
    • , Dandan Liang
    • , Jiajian Liu
    • , Tianlu Chen
    • , Chao Yan
    • , Runmin Wei
    • , Cynthia Rajani
    • , Chengxing Shen
    • , Guoxiang Xie
    • , Zhaoxiang Bian
    • , Houkai Li
    • , Aihua Zhao
    •  & Wei Jia
  • Article
    | Open Access

    The temporal resolution of optical measurements of neural activity has traditionally been limited by the image or volume acquisition rate. Here, the authors describe an analysis that exploits the short duration of neural measurements within each image to extract neural responses at higher temporal resolution than the acquisition rate.

    • Omer Mano
    • , Matthew S. Creamer
    • , Catherine A. Matulis
    • , Emilio Salazar-Gatzimas
    • , Juyue Chen
    • , Jacob A. Zavatone-Veth
    •  & Damon A. Clark
  • Article
    | Open Access

    Deep convolutional neural networks (DCNNs) are able to identify faces on par with humans. Here, the authors record neuronal activity from higher visual areas in humans and show that face-selective responses in the brain show similarity to those in the intermediate layers of the DCNN.

    • Shany Grossman
    • , Guy Gaziv
    • , Erin M. Yeagle
    • , Michal Harel
    • , Pierre Mégevand
    • , David M. Groppe
    • , Simon Khuvis
    • , Jose L. Herrero
    • , Michal Irani
    • , Ashesh D. Mehta
    •  & Rafael Malach
  • Article
    | Open Access

    Cortical responses are highly heterogeneous, making it difficult to describe how they behave as a population. Here, the author overcomes this problem by introducing a geometric approach to study the representation of orientation and its transformation under the presence of a mask.

    • Dario L. Ringach
  • Article
    | Open Access

    In order to perceive moving or changing objects, sensory information must be integrated over time. Here, using a visual sequential metacontrast paradigm, the authors show that integration occurs only when subsequent stimuli are presented within a discrete window of time after the initial stimulus.

    • Leila Drissi-Daoudi
    • , Adrien Doerig
    •  & Michael H. Herzog
  • Article
    | Open Access

    “Genome-wide association studies have identified variants associated with age-related macular degeneration (AMD); however, other than identifying this as a complement mediated inflammatory disease, little biology has emerged. Here, authors used novel computational tools from the Broad Institute to examine the relationship of single-cell transcriptomics and genome-wide association studies (GWAS) in the human retina and demonstrate that GWAS-associated risk alleles associated with AMD are enriched in glia and vascular cells and that human retinal glia are more diverse than previously thought

    • Madhvi Menon
    • , Shahin Mohammadi
    • , Jose Davila-Velderrain
    • , Brittany A. Goods
    • , Tanina D. Cadwell
    • , Yu Xing
    • , Anat Stemmer-Rachamimov
    • , Alex K. Shalek
    • , John Christopher Love
    • , Manolis Kellis
    •  & Brian P. Hafler
  • Article
    | Open Access

    The role of chemoreceptors on vomeronasal neurons are not fully understood. Here the authors show that in mice, the vomeronasal chemoreceptor Fpr3 responds to peptides from the bacterial MgrB protein, and that exposure to these peptides drives an avoidance response.

    • Bernd Bufe
    • , Yannick Teuchert
    • , Andreas Schmid
    • , Martina Pyrski
    • , Anabel Pérez-Gómez
    • , Janina Eisenbeis
    • , Thomas Timm
    • , Tomohiro Ishii
    • , Günter Lochnit
    • , Markus Bischoff
    • , Peter Mombaerts
    • , Trese Leinders-Zufall
    •  & Frank Zufall
  • 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

    Immune cells are shaped by the tissue environment, yet the states of healthy human T cells are mainly studied in the blood. Here, the authors perform single cell RNA-seq of T cells from tissues and blood of healthy donors and show its utility as a reference map for comparison of human T cell states in disease.

    • Peter A. Szabo
    • , Hanna Mendes Levitin
    • , Michelle Miron
    • , Mark E. Snyder
    • , Takashi Senda
    • , Jinzhou Yuan
    • , Yim Ling Cheng
    • , Erin C. Bush
    • , Pranay Dogra
    • , Puspa Thapa
    • , Donna L. Farber
    •  & Peter A. Sims
  • Article
    | Open Access

    In a large prospective cohort of liver transplantation (LT) recipients, the authors identify associations between colonization by multidrug-resistant bacteria (MDRB) and microbiome dysbiosis pre- and post-LT, suggesting colonizing MDRB as an important target for microbiome-informed therapeutic approaches post-LT.

    • Medini K. Annavajhala
    • , Angela Gomez-Simmonds
    • , Nenad Macesic
    • , Sean B. Sullivan
    • , Anna Kress
    • , Sabrina D. Khan
    • , Marla J. Giddins
    • , Stephania Stump
    • , Grace I. Kim
    • , Ryan Narain
    • , Elizabeth C. Verna
    •  & Anne-Catrin Uhlemann
  • Article
    | Open Access

    Elevated inorganic phosphate levels promote excessive parathyroid hormone secretion, which contributes to the aetiology of secondary hyperparathyroidism. Here, the authors show that phosphate directly inhibits the calcium-sensing receptor, the main regulator of parathyroid hormone secretion.

    • Patricia P. Centeno
    • , Amanda Herberger
    • , Hee-Chang Mun
    • , Chialing Tu
    • , Edward F. Nemeth
    • , Wenhan Chang
    • , Arthur D. Conigrave
    •  & Donald T. Ward
  • 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

    Reactive oxygen species (ROS) stimulate GLUT4-mediated glucose transport following contraction of isolated muscle, but it is not clear if this occurs in vivo. Here, the authors show in human volunteers that exercise induces ROS increase in muscle and, using loss of-function animal models, they demonstrate that NOX2 is a major ROS source required to stimulate glucose uptake during exercise.

    • Carlos Henríquez-Olguin
    • , Jonas R. Knudsen
    • , Steffen H. Raun
    • , Zhencheng Li
    • , Emilie Dalbram
    • , Jonas T. Treebak
    • , Lykke Sylow
    • , Rikard Holmdahl
    • , Erik A. Richter
    • , Enrique Jaimovich
    •  & Thomas E. Jensen
  • 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

    Leflunomide is used for the treatment of rheumatoid arthritis. Here, the authors show that effectiveness is limited in patients with higher levels of serum c-reactive protein (CRP). Using animal models, they show that higher CRP induces HIF1a expression, which in turn interferes with Leflunomide signalling, and that effectiveness of the drug is restored when HIF1a is pharmacologically inhibited.

    • Chao Liang
    • , Jie Li
    • , Cheng Lu
    • , Duoli Xie
    • , Jin Liu
    • , Chuanxin Zhong
    • , Xiaohao Wu
    • , Rongchen Dai
    • , Huarui Zhang
    • , Daogang Guan
    • , Baosheng Guo
    • , Bing He
    • , Fangfei Li
    • , Xiaojuan He
    • , Wandong Zhang
    • , Bao-Ting Zhang
    • , Ge Zhang
    •  & Aiping Lu
  • 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

    A challenge in cell therapy for photoreceptor degeneration is inducing the grafted cells to grow and maintain light sensitive outer segments. Here, the authors use optogenetics to circumvent this problem and restore visual function in blind mice.

    • Marcela Garita-Hernandez
    • , Maruša Lampič
    • , Antoine Chaffiol
    • , Laure Guibbal
    • , Fiona Routet
    • , Tiago Santos-Ferreira
    • , Sylvia Gasparini
    • , Oliver Borsch
    • , Giuliana Gagliardi
    • , Sacha Reichman
    • , Serge Picaud
    • , José-Alain Sahel
    • , Olivier Goureau
    • , Marius Ader
    • , Deniz Dalkara
    •  & Jens Duebel
  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is associated with severe neonatal morbidity. Here the authors show, mirroring the NEC phenotype, that IL-23 overexpression in neonates causes malabsorption and decreased expression of intestinal and pancreatic genes mediating food digestion and uptake through IL-22, which directly suppresses pancreatic cell differentiation.

    • Lili Chen
    • , Valentina Strohmeier
    • , Zhengxiang He
    • , Madhura Deshpande
    • , Jovani Catalan-Dibene
    • , Scott K. Durum
    • , Thomas M. Moran
    • , Thomas Kraus
    • , Huabao Xiong
    • , Jeremiah J. Faith
    • , Chhinder P. Sodhi
    • , David J. Hackam
    • , Sergio A. Lira
    •  & Glaucia C. Furtado
  • Article
    | Open Access

    Multiple myeloma is a cancer of the bone marrow that can induce bone disease. Here, the authors profile the transcriptome of bone-lining cells and find a targetable role of bone morphogenetic protein (BMP) signalling in myeloma-induced bone-disease

    • Sarah Gooding
    • , Sam W. Z. Olechnowicz
    • , Emma V. Morris
    • , Andrew E. Armitage
    • , Joao Arezes
    • , Joe Frost
    • , Emmanouela Repapi
    • , James R. Edwards
    • , Neil Ashley
    • , Craig Waugh
    • , Nicola Gray
    • , Erik Martinez-Hackert
    • , Pei Jin Lim
    • , Sant-Rayn Pasricha
    • , Helen Knowles
    • , Adam J. Mead
    • , Karthik Ramasamy
    • , Hal Drakesmith
    •  & Claire M. Edwards
  • Article
    | Open Access

    Increasing TCR cell surface expression can potentiate T cell responses to low-concentrations of antigen. Here the authors identify aminoacids in human TCR variable domains that impact its surface expression, and demonstrate how editing these residues can improve T cell activation and effector function without altering antigen specificity.

    • Sharyn Thomas
    • , Fiyaz Mohammed
    • , Rogier M. Reijmers
    • , Annemarie Woolston
    • , Theresa Stauss
    • , Alan Kennedy
    • , David Stirling
    • , Angelika Holler
    • , Louisa Green
    • , David Jones
    • , Katherine K. Matthews
    • , David A. Price
    • , Benjamin M. Chain
    • , Mirjam H. M. Heemskerk
    • , Emma C. Morris
    • , Benjamin E. Willcox
    •  & Hans J. Stauss
  • Article
    | Open Access

    The biology of the urothelium has been difficult to study given the lack of methods to propagate these cells. Here, the authors generate mouse urothelial organoids derived from bladder urothelial cells with high CD49f/ITGA6 and define what regulates urothelium differentiation, which is PPARγ, EGFR and Notch signalling.

    • Catarina P. Santos
    • , Eleonora Lapi
    • , Jaime Martínez de Villarreal
    • , Laura Álvaro-Espinosa
    • , Asunción Fernández-Barral
    • , Antonio Barbáchano
    • , Orlando Domínguez
    • , Ashley M. Laughney
    • , Diego Megías
    • , Alberto Muñoz
    •  & Francisco X. Real
  • 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

    MR-focused ultrasound can be used to transiently open the blood-brain barrier (BBB). Here, the authors report the results of a first-in-human trial on four patients with amyotrophic lateral sclerosis (ALS), showing that the procedure reversibly permeabilised the BBB in the motor cortex without complications, and suggest that the procedure could in the future be used to increase drug delivery in ALS patients.

    • Agessandro Abrahao
    • , Ying Meng
    • , Maheleth Llinas
    • , Yuexi Huang
    • , Clement Hamani
    • , Todd Mainprize
    • , Isabelle Aubert
    • , Chinthaka Heyn
    • , Sandra E. Black
    • , Kullervo Hynynen
    • , Nir Lipsman
    •  & Lorne Zinman
  • Article
    | Open Access

    Internalized receptors are recycled back to the cell surface, but their precise mechanisms are unclear. Here, the authors show that the flotillin membrane proteins may regulate the transfer of internalized T cell receptors into Rab5 and Rab11-positive endosomes to support its rapid recycling.

    • Gregory M. I. Redpath
    • , Manuela Ecker
    • , Natasha Kapoor-Kaushik
    • , Haig Vartoukian
    • , Michael Carnell
    • , Daryan Kempe
    • , Maté Biro
    • , Nicholas Ariotti
    •  & Jérémie Rossy
  • Article
    | Open Access

    Enamel is the hardest tissue in the body and has been widely studied, yet aspects of its structure remain unclear. Here, the authors report on a study of the orientation and alignment of enamel crystals and challenge previous assumptions.

    • Elia Beniash
    • , Cayla A. Stifler
    • , Chang-Yu Sun
    • , Gang Seob Jung
    • , Zhao Qin
    • , Markus J. Buehler
    •  & Pupa U. P. A. Gilbert
  • Article
    | Open Access

    Stat6 promotes M2 macrophage polarization. Here the authors characterize Trim24-CBP-Stat6 circuit regulating M2 macrophage polarization via Stat6 acetylation, and show it contributes to pro-tumorigenic macrophage activity in mice.

    • Tao Yu
    • , Shucheng Gan
    • , Qingchen Zhu
    • , Dongfang Dai
    • , Ni Li
    • , Hui Wang
    • , Xiaosong Chen
    • , Dan Hou
    • , Yan Wang
    • , Qiang Pan
    • , Jing Xu
    • , Xingli Zhang
    • , Junli Liu
    • , Siyu Pei
    • , Chao Peng
    • , Ping Wu
    • , Simona Romano
    • , Chaoming Mao
    • , Mingzhu Huang
    • , Xiaodong Zhu
    • , Kunwei Shen
    • , Jun Qin
    •  & Yichuan Xiao
  • Article
    | Open Access

    Sexual dimorphism is observed frequently in immune disorders, but the underlying insights are still unclear. Here the authors analyze transcriptome and epigenome changes induced by interferon in various mouse immune cell types, and find only a restricted set of sexual dimorphism genes in innate immunity and macrophages.

    • Shani Talia Gal-Oz
    • , Barbara Maier
    • , Hideyuki Yoshida
    • , Kumba Seddu
    • , Nitzan Elbaz
    • , Charles Czysz
    • , Or Zuk
    • , Barbara E. Stranger
    • , Hadas Ner-Gaon
    •  & Tal Shay
  • 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