Lymphoid tissues

  • Article
    | Open Access

    Natural Killer cell development is controlled by two related transcription factors, Eomes and T-bet. Authors show here that while the two factors share a large proportion of their target genes, they regulate distinct developmental processes by differing in their pattern of expression and in their associated co-factors.

    • Jiang Zhang
    • , Stéphanie Le Gras
    •  & Thierry Walzer
  • Article
    | Open Access

    Development of the T cells requires functions from thymic epithelial cells, whose development and function are epigenetically regulated. Here the authors show that inactivation of the polycomb repressive complex 2 (PRC2) alters the H3K27me3 configuration, reduces TEC functions, reveals a specific TEC subset, and hampers T cell development.

    • Thomas Barthlott
    • , Adam E. Handel
    •  & Georg A. Holländer
  • Article
    | Open Access

    Conventional T cell subsets are selected in the thymus by peptide bearing MHC expressed by cortical epithelial cells, in contrast cortical thymocytes express non-peptide bearing MHC molecules including CD1d and MR1 and select iNKT and MAIT cell populations respectively. Here, the authors generate a novel inducible MHC class-I trasnactivator murine system and suggest the absence of peptide-MHC on thymocytes is involved in the selection of non-peptide specific lymphocytes.

    • Hristo Georgiev
    • , Changwei Peng
    •  & Kristin A. Hogquist
  • Article
    | Open Access

    NK cells control SIV infection in secondary lymphoid tissues in the natural host that typically doesn’t progress toward disease. Here the authors show that this control is associated with terminal NK cell differentiation and improved MHC-E-dependent activity lacking in pathogenic SIV infection.

    • Nicolas Huot
    • , Philippe Rascle
    •  & Michaela Müller-Trutwin
  • Article
    | Open Access

    The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.

    • Jhoanne L. Bautista
    • , Nathan T. Cramer
    •  & Audrey V. Parent
  • Article
    | Open Access

    The thymus is essential for T cell maturation and selection, and thymic defects result in severe immune problems. Here the authors identify a thymus cell population that is expandable in vitro, and can repopulate natural thymic matrix to generate tissue that supports mature T cell development in vitro and in vivo.

    • Sara Campinoti
    • , Asllan Gjinovci
    •  & Paola Bonfanti
  • Article
    | Open Access

    Innate T cells such as iNKT, MAIT and γδ T cells all develop in the thymus, but their differentiation paths are still unclear. Here, the authors show, using single-cell RNA sequencing, that all three cell types develop via shared and branched differentiation paths that are corroborated by additional results from gene-deficient mice and human liver T cells.

    • Minji Lee
    • , Eunmin Lee
    •  & You Jeong Lee
  • Article
    | Open Access

    Migration and homing of B cells to lymph nodes are important for B cell functions, but their regulation is poorly understood. Here, the authors show that B cell-specific deletion of Cosmc results in decreased protein O-glycosylation, loss of B cell homing to both lymphoid and nonlymphoid organs, and altered transendothelial migration implicated in this loss.

    • Junwei Zeng
    • , Mahmoud Eljalby
    •  & Richard D. Cummings
  • Article
    | Open Access

    The origin and diversity of blood vascular endothelial cells (BEC) in lymphoid tissues is unclear. Here, the authors profile murine BECs from peripheral lymph nodes by single cell analysis and identify subsets of cells specialised for immune cell recruitment and vascular homeostasis.

    • Kevin Brulois
    • , Anusha Rajaraman
    •  & Eugene C. Butcher
  • Article
    | Open Access

    T cell tolerance is established in the thymus via interactions with medullary thymic epithelial cells (mTEC) expressing tissue-restricted self antigens. Here, the authors suggest, using new transgenic mouse lines and single cell transcriptome analyses, that specific mTEC subsets are associated with distinct T cell fates.

    • Marie-Ève Lebel
    • , Marie Coutelier
    •  & Heather J. Melichar
  • Article
    | Open Access

    Morphogens such as chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.

    • Jason Cosgrove
    • , Mario Novkovic
    •  & Mark C. Coles
  • Article
    | Open Access

    Thymus is a unique environment hosting the development of many T cell subsets with distinct functions. Here the authors show that medullary thymic epithelial cells (mTEC) are functionally diverse, with LTβR signaling serving differential regulation of mTEC for specific control of multiple lineages of invariant natural killer T cells.

    • Beth Lucas
    • , Andrea J. White
    •  & Graham Anderson
  • Article
    | Open Access

    Immune cells mostly enter lymph nodes (LN) from blood circulation, but whether afferent lymphatics contributes to LN entry is unclear. Here, the authors show, using a photo-convertible reporter, that T cells in afferent lymphatics frequently enter LN and become arrested in the subcapsular sinus, with chemokines and integrins further guiding their migration in the LN.

    • Rieke Martens
    • , Marc Permanyer
    •  & Reinhold Förster
  • Article
    | Open Access

    Lymphatic endothelial cells (LECs) can cross-present antigen to naïve CD8+ T cells, but the significance of this interaction was unclear. Here the authors show that LECs directly induce CD8+ T cell differentiation with memory-like phenotypes, migration patterns and transcriptome, which can later be recalled to promote effector immunity and protection from Listeria infection.

    • Efthymia Vokali
    • , Shann S. Yu
    •  & Melody A. Swartz
  • Article
    | Open Access

    Fibroblastic reticular cells (FRC) are important for lymph node (LN) structure and function. Here the authors show that the YAP/TAZ complex downstream of Hippo signalling regulates FRC commitment and maturation, with YAP/TAZ deficiency impairing FRC differentiation, while hyperactivation of YAZ/TAZ inducing myofibroblastic FRCs and LN fibrosis.

    • Sung Yong Choi
    • , Hosung Bae
    •  & Gou Young Koh
  • Article
    | Open Access

    Thymic epithelial cells (TEC) are essential for the maturation of functional T cells, while thymus size is proportional to the overall output efficiency. Here the authors show, using transcriptome analyses, that mouse fetal TEC maintain a Myc-dependent genetic program to ensure a rapid increase in thymus size, and thereby expedited T cell generation.

    • Jennifer E. Cowan
    • , Justin Malin
    •  & Avinash Bhandoola
  • 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
    •  & Howard T. Petrie
  • Article
    | Open Access

    The white pulp of spleen is an important immune structure dynamically modulated during development and immune responses. Here the authors define, using multi-color lineage tracing and single-cell transcriptome analysis, the subset distribution and differentiation trajectory of fibroblastic reticular cells to serve structural insights for splenic white pulps.

    • Hung-Wei Cheng
    • , Lucas Onder
    •  & Burkhard Ludewig
  • Article
    | Open Access

    Burkitt lymphoma (BL) is the most common pediatric B-cell lymphoma. Here, within the International Cancer Genome Consortium, the authors performed whole genome and transcriptome sequencing of 39 sporadic BL, describing the landscape of mutations, structural variants, and mutational processes that underpin this disease how alterations on different cellular levels cooperate in deregulating key pathways and complexes.

    • Cristina López
    • , Kortine Kleinheinz
    •  & Reiner Siebert
  • Article
    | Open Access

    Protective antibody responses depend critically on proper B cell development and differentiation at multiple stages. Here the authors show that a protein arginine methyltransferase, Prmt5 uses multiples pathways to prevent death of immature B cells, yet modulates, in p53-independent manners, the survival and differentiation of mature B cells.

    • Ludivine C. Litzler
    • , Astrid Zahn
    •  & Javier M. Di Noia
  • Article
    | Open Access

    Human blood cells all develop from haematopoietic stem cells (HSCs), classically thought to be multipotent. Here the authors show, using single-cell RNA-seq and functional assays, that loss of erythroid potential and commitment to the myelo-lymphoid lineage occurs within the purest HSC compartment to date.

    • Serena Belluschi
    • , Emily F. Calderbank
    •  & Elisa Laurenti
  • Article
    | Open Access

    Induction of tolerance in the gut relies on immunomodulatory functions of mesenteric lymph nodes (mLN). Here the authors show that mLN stromal cells receive early microbiota imprinting in the neonatal phase to exhibit long-term, location-specific transcriptional programs for the induction of regulatory T cells and peripheral tolerance.

    • Joern Pezoldt
    • , Maria Pasztoi
    •  & Jochen Huehn
  • Article
    | Open Access

    CD69 competes with S1P1, a chemokine receptor mediating thymocyte egress, for surface expression on thymocytes, but whether CD69 is required for normal thymic development is unclear. Here the authors show that CD69 and S1P1 synergize to control type 2 natural killer (NKT2) cells differentiation by modulating the thymic egress of NKT2 precursor.

    • Motoko Y. Kimura
    • , Akemi Igi
    •  & Toshinori Nakayama
  • Article
    | Open Access

    The commitment of helper and cytotoxic lineages for CD4 and CD8 T cells, respectively, is associated with the regulation of Cd4 gene expression. Here the authors show that an intronic silencer, S4, has differential effects and synergy with the RUNX complex to act on two enhancer elements of the CD4 gene to control T cell lineage commitment in the thymus.

    • Satoshi Kojo
    • , Nighat Yasmin
    •  & Ichiro Taniuchi
  • Article
    | Open Access

    The expression of CD4, a critical co-receptor providing T cell help in adaptive immunity, is finely tuned during development. Here the authors show that two enhancer elements, E4p and the newly-defined E4m, coordinate the expression and heritable demethylation of Cd4 in thymocytes but are dispensable for its sustained expression in peripheral T cells.

    • Priya D. Issuree
    • , Kenneth Day
    •  & Dan R. Littman
  • Article
    | Open Access

    Memory B cells need to be reactivated to produce high affinity antibody responses on subsequent antigen encounters. Here the authors show that memory B cells localise to lymph node subcapsular proliferative foci (SPF), which have distinct properties from the germinal centre, for rapid expansion and the induction of B memory responses.

    • Imogen Moran
    • , Akira Nguyen
    •  & Tri Giang Phan
  • Article
    | Open Access

    Tumor neoantigens can be drained to the lymph nodes, but the nature and the significance of the induced immune responses are still unclear. Here the authors use a mouse genetic tumor model to show that tumor-specific CD4 T cells can become anergic or suppressive in the draining lymph node to modulate tumor immunity.

    • Ruby Alonso
    • , Héloïse Flament
    •  & Olivier Lantz
  • Article
    | Open Access

    Non-circulating, tissue-resident T cells have been reported for non-lymphoid organs, but their characterization and regulation in secondary lymphoid organs (SLO) are still lacking. Here the authors show that age and microbiota both exert SLO-specific effects for the various tissue-resident T cell subsets.

    • Aurélie Durand
    • , Alexandra Audemard-Verger
    •  & Bruno Lucas
  • Article
    | Open Access

    Longitudinal imaging of bone marrow would shed insight into long-term cellular dynamics within this compartment. Here, the authors develop a multi-photon imaging approach for the mouse femur and reveal extensive vascular plasticity within the bone marrow during bone healing and steady-state homeostasis.

    • David Reismann
    • , Jonathan Stefanowski
    •  & Raluca A. Niesner
  • Article
    | Open Access

    Viral infection and vaccination both induce lasting persistence of antigens for protective responses. Here the authors show that migratory dendritic cells, independent of the transcription factor BatF3 for their development, contribute to “archived antigen” exchange with lymphatic endothelial cells.

    • Ross M. Kedl
    • , Robin S. Lindsay
    •  & Beth A. Jirón Tamburini
  • Article
    | Open Access

    Mouse γδ T cells have diverse functional subsets, but how these subsets are programmed during their development is still unclear. Here the authors show that three surface markers, CD117, CD200 and CD371, refine the development of γδ T cells in the thymus into three pathways programming distinct γδ T cell subsets.

    • Terkild Brink Buus
    • , Niels Ødum
    •  & Jens Peter Holst Lauritsen
  • Article
    | Open Access

    CD4 and CD8 T cells develop in the thymus with their transcription programs controlled by ThPOK and Runx3, respectively. Here the authors show that a pre-commitment event modulated by the transcription factor, Bcl11b, is required for the proper expression of ThPOK and Runx3 and correct CD4/CD8 lineage commitment.

    • Satoshi Kojo
    • , Hirokazu Tanaka
    •  & Ichiro Taniuchi
  • Article
    | Open Access

    The growth of lymph nodes in response to infection requires lymphangiogenesis. Dubey et al. show that the mesenteric lymph node lymphangiogenesis upon helminth infection depends on the signaling loop between the B and fibroblastic reticular cells (FRCs), whereby the FRCs respond to lymphotoxin secreted by B cells by releasing B cell activating factor.

    • Lalit Kumar Dubey
    • , Praneeth Karempudi
    •  & Nicola L. Harris
  • Article
    | Open Access

    Foxn1 is involved in thymic epithelial cell (TEC) and CD8+T cell development. Here the authors show this development requires Foxn1 binding proximal to, and inducing transcription of, the gene encoding β5t in cortical TECs.

    • Muhammad Myn Uddin
    • , Izumi Ohigashi
    •  & Yousuke Takahama
  • Article
    | Open Access

    Fat-associated lymphoid clusters (FALC) in the serous cavities house rapid IgM-producing B1 cells, but how the clusters are activated to respond to infection is unclear. Here the authors show that in response to lung inflammation or pleural nematode infection adipose stromal cell-derived IL-33 activates ILC2s to produce IL-5, thus driving the B1 response in the FALCs.

    • Lucy H. Jackson-Jones
    • , Sheelagh M. Duncan
    •  & Cécile Bénézech
  • Article
    | Open Access

    Jmjd6 is a dioxygenase that catalyses lysyl hydroxylation of splicing regulatory proteins. Here the authors show that Jmjd6 directs splicing of a central tolerance regulator Aire in medullary thymic epithelial cells, and that Jmjd6 deficiency leads to loss of Aire and multi-organ autoimmunity in mice.

    • Toyoshi Yanagihara
    • , Fumiyuki Sanematsu
    •  & Fukui Yoshinori
  • Article
    | Open Access

    Proteasomes digest intracellular proteins into peptides that are then presented to lymphocytes as antigens. Here the authors show that a thymic epithelium-specific proteasome subunit cuts model proteins in a pattern favouring their weak binding to T cell receptor, and thus T cell positive selection.

    • Katsuhiro Sasaki
    • , Kensuke Takada
    •  & Shigeo Murata
  • Article
    | Open Access

    SHP-1 signalling is required for the normal development of B lymphocytes but its role in the terminal differentiation of these cells has not been fully established. Here, the authors show that SHP-1 ablation impairs the establishment of long-lived bone marrow-resident plasma cells due to aberrant integrin activation.

    • Yan-Feng Li
    • , Shengli Xu
    •  & Kong-Peng Lam
  • Article |

    Thymic stromal lymphopoietin is an important initiator of Th2 responses, but, to date, little is known about how it drives the immune cascade in the tissue microenvironment in vivo. Here, the authors show that skin thymic stromal lymphopoietin orchestrate interactions between immune cells, leading to Th2 priming.

    • Juan Manuel Leyva-Castillo
    • , Pierre Hener
    •  & Mei Li
  • Article
    | Open Access

    T cells learn to tolerate self-antigens in the thymus, where self-peptides are presented by thymic antigen-presenting cells. Here, the authors present an ex vivomass spectrometric analysis of the self-peptide repertoire associated with MHC I and II in human thymic tissue.

    • Eleni Adamopoulou
    • , Stefan Tenzer
    •  & Christina Stoeckle