Lymphocytes articles within Nature Communications

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  • Article
    | Open Access

    The clinical success of anti- αEβ7 antibody Etrolizumab for Crohn’s disease is less than what is expected based on proof-of-concept studies. Here authors show, by characterization of T cells from Etrolizumab-treated patients, in vitro functional assays and reanalysis of public single cell datasets on Etrolizumab-treated patients, that at high level of T cell activation, which characterises T cells in Crohn’s disease, E-Cadherin-αEβ7 interactions become resistant to Etrolizumab inhibition.

    • Maximilian Wiendl
    • , Mark Dedden
    •  & Sebastian Zundler

  • Article
    | Open Access

    The presence of CD8+ T cells in the cytoplasm of biliary epithelial cells (BEC) has been associated with primary biliary cholangitis. Here, the authors demonstrate that CD8+ T cells invade BEC using a mechanism that is dependent on cytoskeletal rearrangements and E-cadherin:β-catenin interactions.

    • Scott P. Davies
    • , Vincenzo Ronca
    •  & Ye H. Oo

  • Article
    | Open Access

    Detection of neoepitopes from tumours is time consuming and requires the integration of genomic and/or RNA sequencing expression data. Here, the authors propose a machine learning method to enable direct identification of additional, tumour-specific sequences using mass spectrometry through integration of de novo peptide sequencing scores, MHC class I binding prediction, and peptide retention time prediction.

    • Hanqing Liao
    • , Carolina Barra
    •  & Nicola Ternette

  • Article
    | Open Access

    The T cell receptor signalosome integrates multiple positive and negative regulatory elements to finetune the response and limit harmful inflammation. Here authors show a regulatory cascade of T cell activation, in which DUSP22 negatively regulates UBR2, which is an activator of the kinase Lck via K63 ubiquitination.

    • Ying-Chun Shih
    • , Hsueh-Fen Chen
    •  & Tse-Hua Tan

  • Article
    | Open Access

    Il-10-expressing B cells play a pivotal role in immune homeostasis, but little is known about the factors and pathways that affect the development of this heterologous population of regulatory B cells. Here authors show in a mouse model that in embryonic life, soluble IgM restrains the expansion of Il-10-positive B cells, via utilizing FcµR and other putative receptors.

    • Shannon Eileen McGettigan
    • , Lazaro Emilio Aira
    •  & Gudrun F. Debes

  • Article
    | Open Access

    Specialised pro-resolving lipid mediators can reduce inflammatory responses and may be active in lymphedema. Here the authors show that in a mouse model 15-LO derived lipid mediators are reduced during inflammation and that a lack of the 15-LO producing enzyme aggravated disease and addition of 15-LO enzyme or Treg cells reduced disease.

    • A. Zamora
    • , M. Nougué
    •  & B. Garmy-Susini

  • Article
    | Open Access

    Modulation of regulatory T cells (Treg) in the tumour environment is a potential avenue to bolster anti-tumor immunity. Here Liu et al show that perturbation of the negative feedback loop involving STAT1- IFITM3 influences anti-tumor immunity, and that IFITM3 or STAT1 deficiency resulting in the fragility of tumor-infiltrating Treg cells.

    • Xinnan Liu
    • , Weiqi Zhang
    •  & Bin Li

  • Article
    | Open Access

    B cell activation and differentiation entails metabolic remodelling, involving differential utilisation of monocarboxylates such as L-lactate and pyruvate. Here authors show by B-cell-specific genomic deletion of monocarboxylate transporter 1 (MCT1) that the consequential scarcity of pyruvate results in decreased acetylation of Histone H3 at K27, leading to decreased AID transcription and deficient class switching to IgG.

    • Wenna Chi
    • , Na Kang
    •  & Ligong Chen

  • Article
    | Open Access

    The ability of BCG vaccination to prevent pulmonary tuberculosis could be improved by targeting mucosal immunity within the lung. Here the authors compare latent Mtb-infected donors with intradermal or oral BCG vaccine recipients to show distinct systemic and pulmonary immune responses are induced by differing routes of natural infection or vaccination.

    • Richard F. Silver
    • , Mei Xia
    •  & Daniel F. Hoft

  • Article
    | Open Access

    Marking of recently activated T cells may help further our understanding of immunity against Mycobacterium tuberculosis (Mtb). Here the authors use Nur77-GFP reporter mice infected with Mtb and systems data approaches to implicate OX40 as a marker for recently activated, functionally and transcriptome-wise distinct CD4 T cells, and as a potential target for immunotherapy.

    • Abigail R. Gress
    • , Christine E. Ronayne
    •  & Tyler D. Bold

  • Article
    | Open Access

    The ability of T cells to migrate is a central component of their functionality and is known to require WNK1 kinase that is linked to the influx of ions into the cell. Here the authors show that T cell migration requires WNK1 mediated ion and water influx to swell the membrane of the leading edge and support actin polymerisation and forward motility.

    • Leonard L. de Boer
    • , Lesley Vanes
    •  & Victor L. J. Tybulewicz

  • Article
    | Open Access

    Nasally delivered live attenuated influenza vaccines (LAIV) have been shown to be effective in vaccine trials yet immune responses are mostly measured in blood. Here the authors report a clinical trial in young adults and measure immune responses in the mucosa and blood to identify compartmentalised responses.

    • Ryan S. Thwaites
    • , Ashley S. S. Uruchurtu
    •  & Peter J. M. Openshaw

  • Article
    | Open Access

    Invariant natural killer T (NKT) cells are defined into subset based on transcription expression and cytokine production, but differences in the subset distributions of these cells are seen between inbred mouse strains. Here the authors show that CD1d mediated TCR signals along with intrinsic signals impact this strain specific difference in the composition of the NKT cell compartment.

    • Ludivine Amable
    • , Luis Antonio Ferreira Martins
    •  & Kamel Benlagha

  • Article
    | Open Access

    Follicular helper T cells play critical roles in the formation of high affinity antibody responses, but the signals involved in the development of these cells after initial differentiation are poorly understood. Here Podestà, Cavazzoni and colleagues characterise transitionary phases of follicular helper T cell development and how progression through these stages is linked to humoral immunity.

    • Manuel A. Podestà
    • , Cecilia B. Cavazzoni
    •  & Peter T. Sage

  • Article
    | Open Access

    γδ T cells are known to recognize phosphoantigen in the context of butyrophilins (BTN), yet the molecular rules underlying this phenomenon are unclear. Here, the authors demonstrate that a distinct topology of B30.2 and IgV domains within BTN3A complexes promotes antigen sensing and that the juxtamembrane region controls BTN complex formation.

    • Mohindar M. Karunakaran
    • , Hariharan Subramanian
    •  & Thomas Herrmann

  • Article
    | Open Access

    Understanding T cell behaviour in cancers is vital for improving immunotherapies. Here, the authors present spatially resolved T cell receptor sequencing (SPTCR-seq), a technology that annotates T cell receptors within the tumour ecosystem.

    • Jasim Kada Benotmane
    • , Jan Kueckelhaus
    •  & Dieter Henrik Heiland

  • Article
    | Open Access

    The use of single cell sequencing has enabled more detailed analysis of the immune response to infection. Here the authors characterise the immune response to malaria infection in an endemic region using single cell transcriptomics indicating regulatory signatures associated with infection.

    • Nicholas L. Dooley
    • , Tinashe G. Chabikwa
    •  & Michelle J. Boyle

  • Article
    | Open Access

    Environmental factors such as diet have been shown to be involved with the development of colitis. Here the authors show that L-tryptophan promotes the development of GPR15+ Treg cells via the host IDO1/2 pathway and that tryptophan consumption in mice reduces severity of colitis in a C. rodentium mouse model.

    • Nguyen T. Van
    • , Karen Zhang
    •  & Sangwon V. Kim

  • Article
    | Open Access

    Mathematical tools can be used to help identify pathological features from images of diseased lungs. Here, the authors used mathematical tools combined with high resolution multiplex imaging mass cytometry to show an association between immature neutrophils, CD8 T cells and proliferating alveolar epithelial cells in areas of maximal alveolar damage in COVID-19 lungs.

    • Praveen Weeratunga
    • , Laura Denney
    •  & Ling-Pei Ho

  • 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

    Innate immunity represents the first line of defence against pathogens, but certain innate cells are capable of memory formation, albeit with different and lesser-known mechanisms than adoptive immune cells. Here authors show that Themis2 regulates both memory NK cell development and function, via distinct downstream pathways.

    • Tsukasa Nabekura
    • , Elfira Amalia Deborah
    •  & Akira Shibuya

  • Article
    | Open Access

    Cell lineage specification involves substantial chromatin conformation reorganization. Here, the authors integrate in-situ Hi-C and PLAC-seq to map the dynamic changes in 3D chromatin structure during Treg cell differentiation. Furthermore, the authors further characterize the role of Foxp3 in the establishment of Treg-specific chromatin interactions by different Foxp3-mutant mouse lines.

    • Zhi Liu
    • , Dong-Sung Lee
    •  & Jesse R. Dixon

  • Article
    | Open Access

    Deep learning frameworks require large human-annotated datasets for training and the resulting ‘black box’ models are difficult to interpret. Here, the authors present Kartezio; a modular Cartesian Genetic Programming-based computational strategy that generates fully transparent and easily interpretable image processing pipelines.

    • Kévin Cortacero
    • , Brienne McKenzie
    •  & Sylvain Cussat-Blanc

  • Article
    | Open Access

    Although T cells proliferate at an exceptionally fast rate following activation, the mechanisms sustaining such fast proliferation remain unclear. Here, the authors demonstrate that c-Myc upregulates the E3 ubiquitin ligase Cul4b to reduce replication stress in CD8+ T cells, allowing massive clonal expansion and viral clearance.

    • Asif A. Dar
    • , Dale D. Kim
    •  & Paula M. Oliver

  • Article
    | Open Access

    Uterine natural killer (NK) cells support tissue homeostasis in the uterus during pregnancy, but it is not fully known how they differentiate into potentially cytotoxic effector cells while avoiding tissue damage. Here authors show that Il21 receptor signalling via STAT3 activation governs their differentiation, while an apoptotic cell death program ensures that harm is limited.

    • Mengwei Han
    • , Luni Hu
    •  & Chao Zhong

  • Article
    | Open Access

    The function of B cells in peripheral blood and secondary lymphoid organs has long been appreciated but whether and how they contribute to tissue immune homeostasis is lesser known. Non-lymphoid organs harbour tissue-resident B cells that include a substantial population of B-1 cells and promote homeostatic anti-inflammatory macrophage polarization via IL-10, with profound effects on bacterial clearance during local infection.

    • Ondrej Suchanek
    • , John R. Ferdinand
    •  & Menna R. Clatworthy

  • Article
    | Open Access

    Increasing evidence suggests that antigen presentation by B cells is critical to the initiation of autoimmunity. Here, the authors demonstrate that tolerance breakdown is initiated outside of germinal centres and that B cells can directly instruct T cells to break tolerance and propagate autoimmune responses.

    • Cecilia Fahlquist-Hagert
    • , Thomas R. Wittenborn
    •  & Søren E. Degn

  • Article
    | Open Access

    CD4+ T cells have been shown to be important in CD8+ T cell responses through a process of DC:T cell interaction. Here the authors further characterise this DC:T cell interaction and show that after CD4+ T cell help these post-synaptic DCs have increased lipid peroxidation and increased MHC class I proteins associated with increased cross-presentation function.

    • Diego Calzada-Fraile
    • , Salvador Iborra
    •  & Francisco Sánchez-Madrid

  • Article
    | Open Access

    Cancer immune therapy utilizing interleukin 15 (Il-15) is hampered by the short half-life and systemic toxic effects of the cytokine. Here authors introduce a biomimetic nanovaccine, in which Il-15 and tumor-associated antigenic peptide/MHC-I complexes are co-anchored to cell membrane vesicles of dendritic cell origin, which elicits antigen-specific T cell response leading to superior anti-tumour effect in syngeneic mouse tumour models.

    • Kaiyuan Wang
    • , Xuanbo Zhang
    •  & Jin Sun

  • Article
    | Open Access

    HIV-1 infection is known to impact the gut mucosa, effecting the microbiota and immune system, but early antiretroviral therapy is linked to partial reversal of this phenomena. Here the authors explore the impact of early commencement of antiretroviral therapy and show this can limit the abnormal responses of intestinal B cells associated with HIV-1 infection.

    • Cyril Planchais
    • , Luis M. Molinos-Albert
    •  & Hugo Mouquet

  • Article
    | Open Access

    γδ T cells are unique T lymphocytes with cytotoxic functions, targeting infections and tumours. Here authors show that the target killing function of γδ T cells is tightly regulated at the level of the availability of lytic molecules granzyme B and perforin.

    • Patrick A. Sandoz
    • , Kyra Kuhnigk
    •  & Björn Önfelt

  • Article
    | Open Access

    Chimeric antigen receptor T (CAR-T) cells represent an emerging form of immune therapy but success, especially in solid tumors, is limited by the scarcity of suitable target epitopes. Here authors show that a distinct epitope motif on the transmembrane protein B7-H3, recognized by a camel nanobody, triggers robust activation and anti-tumor function in cognate CAR-T cells.

    • Dan Li
    • , Ruixue Wang
    •  & Mitchell Ho

  • Article
    | Open Access

    Effective CD8+ T cell immunity requires the generation of a long-lived memory pool and the maintenance of a non-exhausted effector T cell pool. The implementation of immune checkpoint blockade can reduced levels of exhaustion but lacks the ability to support memory formation in the effector pool. Here the authors suggest a role for Let-7 in the enhancement of the anti-tumor CD8+ T cell response by supporting memory via modulation of metabolic and differentiation state.

    • Alexandria C. Wells
    • , Kaito A. Hioki
    •  & Leonid A. Pobezinsky

  • Article
    | Open Access

    Regulatory T cells, and to certain extent other T cell subsets, limit the immune response to avoid harmful inflammation and tissue damage. Here authors identify a surface molecule, Lrig1, that is directly responsible for the suppressive function in regulatory T cells and in Il-17-producing helper T cells.

    • Jae-Seung Moon
    • , Chun-Chang Ho
    •  & Sang-Kyou Lee

  • Article
    | Open Access

    How the immune response is involved in the response to multiple myeloma after treatment is not fully understood. Here the authors investigate how lenalidomide treatment in newly diagnosed MM patients affects the immune microenvironment in the blood and bone marrow and compare between responses to treatment.

    • David G. Coffey
    • , Francesco Maura
    •  & Ola Landgren

  • Article
    | Open Access

    The most appreciated producers of pathogenic type-2 cytokines in asthma are T helper 2 cells and group 2 innate lymphoid cells, however, CD8+ cytotoxic T cells are also capable of secreting these mediators. Authors here show that IL-33, a cytokine that is produced by the inflammatory microenvironment, promotes type-2 cytotoxic T cell development, which is linked to asthma exacerbations.

    • Esmee K. van der Ploeg
    • , Lisette Krabbendam
    •  & Ralph Stadhouders

  • Article
    | Open Access

    B cells pursue specific genetic programs to facilitate downstream cellular functions. Here the authors identify, using a combination of proteomic, transcriptomic and functional analyses, a group of mRNAs related to early activation and antibody production that are expressed in B cells without corresponding proteins, hinting a ‘poised’ state of B cells.

    • Fiamma Salerno
    • , Andrew J. M. Howden
    •  & Martin Turner

  • Article
    | Open Access

    CD226 provides a co-stimulatory signal to the T cell receptor during activation, and TIGIT is believed to inhibit this process by competing for the CD226 ligand CD155. Here authors show that ligand binding induces dense nanocluster formation by TIGIT which initiates intrinsic, CD226 independent inhibitory signals, proximal to T cell receptor signalling.

    • Jonathan D. Worboys
    • , Katherine N. Vowell
    •  & Daniel M. Davis

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