Lymphoid tissues articles within Nature Communications

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  • Article
    | Open Access

    Regulation of thymocyte development by RNA-binding proteins is not fully characterized. Here the authors show the RBP ARPP21 interacting with the Rag1 3’-UTR to promote Rag1 expression, TCR rearrangement and an increased diversity of the TCR repertoire and that ARPP21 is down regulated by TCR stimulation.

    • Meng Xu
    • , Taku Ito-Kureha
    •  & Vigo Heissmeyer

  • Article
    | Open Access

    The molecular mechanisms that maintain thymic epithelial cell (TEC) identity throughout life are incompletely understood. Here, the authors demonstrate that the transcription factor, Ovol2, maintains post-natal TECs by preventing their epithelial-to-mesenchymal transition.

    • Xue Zhong
    • , Nagesh Peddada
    •  & Bruce Beutler

  • Article
    | Open Access

    Although thymic function declines with age, the thymus also has the ability to regenerate following injury. Here, the authors demonstrate that IL-33 and type-2 innate lymphoid cells trigger the expansion of eosinophils following radiation injury, which in turn produce IL-4 to stimulate the recovery of the thymus mesenchyme during thymus regeneration.

    • Emilie J. Cosway
    • , Kieran D. James
    •  & Graham Anderson

  • Article
    | Open Access

    T cell development requires functionally diverse thymic epithelial cell (TEC) populations performing specific functions. Here, using massively parallel flow cytometry and machine learning, the authors examine in mice the TEC compartment from the perinatal period to adulthood, identify novel phenotypic markers and characterize the function of perinatal cortical TEC.

    • Fabian Klein
    • , Clara Veiga-Villauriz
    •  & Georg A. Holländer

  • Article
    | Open Access

    It is debated how follicular helper T (Tfh) cells versus central memory CD4+ T cells arise from similar precursors, and little is known about the regulation of germinal-centre (GC)-Tfh cell differentiation. Here, authors establish markers in the early precursor stage that distinguish between the GC-Tfh and memory T cell fates and identify an important mechanism that regulates the competitive fitness of the GC-Tfh cells.

    • Fangming Zhu
    • , Ryan J. McMonigle
    •  & Hui Hu

  • Article
    | Open Access

    Sentinel lymph nodes (SLNs) represent the sites where micro-metastasis can first develop, however they are also important to mount effective anti-tumor immune responses. Here the authors describe the design of a flex-patch loaded with anti-PD-1 antibodies and immuno-adjuvant nanosheets, layered double hydroxide, to fuel anti-tumor immune response in the SLN for postsurgical breast cancer adjuvant therapy.

    • Bei Li
    • , Guohao Wang
    •  & Yunlu Dai

  • Article
    | Open Access

    Although the importance of thymic epithelial cells (TEC) in thymus physiology is established, the development of functionally diverse TEC populations remains incompletely understood. Here, using fate-mapping experiments in the embryonic thymus, the authors identify keratin19+ multipotent progenitor cells that support medullary TEC diversity in adulthood.

    • Beth Lucas
    • , Andrea J. White
    •  & Graham Anderson

  • Article
    | Open Access

    IL-2/anti-IL-2 antibody complexes have been shown to facilitate the process of graft acceptance in transplantation. Here the authors use a mouse allograft model to show that IL-2 complexes promote graft acceptance and formation of inducible lymphoid structures containing Treg cells in transplanted lungs.

    • Yoshito Yamada
    • , Tuan Thanh Nguyen
    •  & Onur Boyman

  • Article
    | Open Access

    Beiging and thermogenesis in white adipose tissue (WAT) is an important adaptive response to cold exposure, but how the brain senses cold and subsequently induces beiging remains unclear. Here, the authors show that sympathetic nerves stimulate lymph nodes to release IL-33, thereby mediating cold-induced beiging of WAT.

    • Lai Yee Cheong
    • , Baile Wang
    •  & Aimin Xu

  • Article
    | Open Access

    Circadian rhythms have been shown to influence immune responses, but it is unclear whether this influences responses to vaccines. Here the authors show that dendritic cells migrate in a circadian rhythm meaning that interactions with T cells are altered leading to differential vaccine responses.

    • Louise Madeleine Ince
    • , Coline Barnoud
    •  & Christoph Scheiermann

  • Article
    | Open Access

    Lymph nodes in various locations of the body differ in their cell composition and gene expression signatures. Here authors show that the rapid postnatal expansion of lymph nodes is governed by CD34 + stromal cells and fibroblastic reticular stromal cell progenitors, distinguished by intrinsic, microbiome-independent core epigenetic blueprints.

    • Joern Pezoldt
    • , Carolin Wiechers
    •  & Jochen Huehn

  • Article
    | Open Access

    The transcription factor MYB has been shown to regulate haematopoietic stem cells but there could be lineage specific enhancers. Here, using lineage tracing and single cell sequencing the authors characterise a Myb −68 enhancer that regulates the differentiation of mast cells and basophils.

    • Takayoshi Matsumura
    • , Haruhito Totani
    •  & Toshio Suda

  • Article
    | Open Access

    Knowledge about the ontogeny of T cells in the thymus relies heavily on mouse studies because of difficulty to obtain human material. Here the authors perform a single cell analysis of thymocytes from human fetal and paediatric thymic samples to characterise the development of human γδ T cells in the thymus.

    • Guillem Sanchez Sanchez
    • , Maria Papadopoulou
    •  & David Vermijlen

  • Article
    | Open Access

    Thymic epithelial tumours represent a heterogenous group of malignancies with varied immune cell infiltration and prognosis. Here authors systematically analyze the phenotypes of both epithelial and immune cells that form these tumours, and identify three major subtypes with different T cell involvement that might affect prognosis.

    • Zhongwei Xin
    • , Mingjie Lin
    •  & Pin Wu

  • Article
    | Open Access

    Myasthenia Gravis and thymoma are frequently associated with patients suffering from both diseases. Here the authors perform single cell sequencing of thymoma and find that there are autoimmune antigens such as neuromuscular proteins expressed aberrantly in neuromuscular mTECs in patients with both diseases.

    • Yoshiaki Yasumizu
    • , Naganari Ohkura
    •  & Hideki Mochizuki

  • Article
    | Open Access

    Activated B cell enter germinal centers (GC) to become plasma cells and memory B cells. Here the authors show that some memory B cells recycle to GC via CCL-21 mediated chemotaxis to deliver antigens from the lymph node subcapsular sinus (SCS) to potentially contribute to affinity maturation and antigenic drift.

    • Yang Zhang
    • , Laura Garcia-Ibanez
    •  & Kai-Michael Toellner

  • Article
    | Open Access

    Fibroblastic reticular cells (FRCs) support localisation of immune cells in secondary lymphoid tissues but less is known about the lamina propria. Here the authors use scRNA-seq and intestinal infection to characterise FRCs in the intestinal lamina propria and show specialised niches that foster innate lymphoid cells during homeostasis and infection.

    • Hung-Wei Cheng
    • , Urs Mörbe
    •  & Burkhard Ludewig

  • Article
    | Open Access

    T cells are selected in the thymus, through interaction with self-antigens, to remove autoreactive cells. Here the authors show that a specialized thymic dendritic cell subset juxtaposes to microvessels, requires CX3CR1/CX3CL1 for this positioning, and has processes extruding into the blood stream to sample soluble macromolecules and assist in T cell selection.

    • Elisabeth H. Vollmann
    • , Kristin Rattay
    •  & Ulrich H. von Andrian

  • 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

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