Innate lymphoid cells articles within Nature Communications

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  • Article
    | Open Access

    RORγt+ group 3 innate lymphoid cells are intimately involved in intestinal homeostasis, their dysregulation is linked to inflammatory gut diseases. Here the authors show that dysregulated Wnt/β-catenin signalling contributes to disturbed regulation of group 3 innate cells and intestinal inflammation.

    • Jiacheng Hao
    • , Chang Liu
    •  & Xiaohuan Guo

  • Article
    | Open Access

    Combination of BET inhibitors (BETi) with immunotherapy has been reported to be synergic for the treatment of non-small cell lung carcinoma (NSCLC). Here, the authors show that BETi-induced epigenetic reprogramming downregulates the expression of NK cell inhibitory receptors on NK cells, increasing their activation and cytotoxicity against NSCLC.

    • Francesca Reggiani
    • , Giovanna Talarico
    •  & Valentina Sancisi

  • Article
    | Open Access

    Natural killer (NK) cell maturation and function are regulated by multiple transcription factors (TF), but detailed molecular insights are scarce. Here the authors show that a TF, Eomes, is important for NK cell responses and cancer surveillance, in which Eomes expression is regulated by gp96 and Trim28 via the ubiquitination and degradation pathways.

    • Yuxiu Xu
    • , Xin Li
    •  & Songdong Meng

  • Article
    | Open Access

    Idiopathic Pulmonary Fibrosis (IPF) consists of lung inflammation and collagen deposition leading to reduced lung function and non-inducible mouse models are needed. Here the authors show a spontaneous mouse IPF model where Ifngr1-/-Rag2-/- mice show enhanced ILC2 activation and function along with pathology similar to IPF.

    • Natsuko Otaki
    • , Yasutaka Motomura
    •  & Kazuyo Moro

  • Article
    | Open Access

    Paneth cell metaplasia (PCM) typically arises in diseases intrinsic to the gastrointestinal tract; however, whether extra intestinal diseases can trigger PCM and the mechanistic pathway by which PCM develops is unknown. Herein, the authors show in an inducible murine model of chronic myelogenous leukaemia that a systemic inflammatory state can trigger IL-33- mediated IL-9 production that leads to small intestinal remodelling and PCM.

    • Chengyin Yuan
    • , Aditya Rayasam
    •  & William R. Drobyski

  • Article
    | Open Access

    Mucosal associated invariant T (MAIT) cells reside in barrier organs, but their contribution to inflammatory processes in the kidneys is not fully known. Here authors find by single cell RNA sequencing that among the different MAIT cell subtypes found at steady state, a population with MAIT17 signature is expanded in both human crescentic glomerulonephritis and its mouse model, and these cells may play protective role in the disease.

    • Ann-Christin Gnirck
    • , Marie-Sophie Philipp
    •  & Jan-Eric Turner

  • 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

    Within gastrointestinal tissues, tuft cells, a rare population of chemo-sensory epithelial cells, can promote the activation of type 2 innate lymphoid cells (ILC2s). Here the authors show that tuft cells and ILC2s are increased during gastric cancer development and that the pharmacologic inhibition of tuft cell derived IL25 or ILC2-produced IL13 reduces gastric tumor growth.

    • Ryan N. O’Keefe
    • , Annalisa L. E. Carli
    •  & Michael Buchert

  • Article
    | Open Access

    The regulation and intracellular transport of Ca2+ in immune cells involves Ca2+ release-activated Ca2+ (CRAC) channels. Here the authors show targeting CRAC components Orai1 and Orai2 modulates pulmonary ILC2 cells altering their metabolism, function and is linked to alleviation of immunopathology in a murine model of allergic airway disease.

    • Emily Howard
    • , Benjamin P. Hurrell
    •  & Omid Akbari

  • Article
    | Open Access

    Allergic asthma is episodic and associated with seasonal changes which may have links with UV exposure levels. Here the authors propose a link between UVB exposure and ILC2 function through α-MSH released from the pituitary gland which accumulates in the serum and alters ILC2 function through the MC5R receptor.

    • Yuying Huang
    • , Lin Zhu
    •  & Bing Sun

  • Article
    | Open Access

    Liver cirrhosis is characterised by extensive fibrosis of the liver, and understanding the underpinning immunological processes is important in designing intervention. Here authors show that Mucosal-Associated Invariant T cells are instrumental to controlling the balance between profibrogenic and restorative macrophages and inhibiting their activation might reverse liver fibrosis.

    • Morgane Mabire
    • , Pushpa Hegde
    •  & Sophie Lotersztajn

  • Article
    | Open Access

    The developmental process of group 2 innate lymphoid cells (ILC2) involves migration between different internal organs. Here the authors show that ILC2s migrate from the lung to the intestine to undergo maturation after treatment with IL-33 and that lung and intestine ILC2s have a different phenotype.

    • Min Zhao
    • , Fei Shao
    •  & Shuo Wang

  • Article
    | Open Access

    Innate lymphoid cells (ILC) are involved with different immune responses. Here the authors show that Interferon regulatory factor 1 (IRF1) is important for intestinal ILC3 accumulation during Citrobacter rodentium infection and promotes release of the protective cytokine IL-22 and response to IL-23.

    • Angelika Schmalzl
    • , Tamara Leupold
    •  & Stefan Wirtz

  • Article
    | Open Access

    Besides hepatocytes, resident immune cells of the liver are also contributing to the body’s energy homeostasis. Here authors show that group 2 innate lymphoid cells interact with a specific set of hepatocytes in suppressing gluconeogenesis and regulate blood glucose levels via Interleukin-13 signalling.

    • Masanori Fujimoto
    • , Masataka Yokoyama
    •  & Tomoaki Tanaka

  • Article
    | Open Access

    The function of T regulatory cells in the tissue fibrosis in chronic pancreatitis is not fully understood. Here the authors use a mouse model of chronic pancreatitis to show that Treg cells reduce IL-4 mediated chronic inflammation in the pancreas associated with M2-like macrophages in vivo.

    • Juliane Glaubitz
    • , Anika Wilden
    •  & Matthias Sendler

  • Article
    | Open Access

    Innate lymphoid cells (ILC) are effector cells that rapidly respond to immune evading stimuli, and despite their functional diversity arise from common precursors. Authors here show how the Notch signalling pathway orchestrates ILC development from circulating human ILC precursors via RORC and its target IL-23R.

    • Carys A. Croft
    • , Anna Thaller
    •  & James P. Di Santo

  • Article
    | Open Access

    Cigarette smoking may exacerbate asthma, but the underlying mechanisms have not been studied extensively in human patients. Here authors show that type 3 innate lymphoid cells with activated phenotypes are found in the sputum and blood of smokers in higher frequencies, which might result in the aggravation of asthma.

    • Jongho Ham
    • , Jihyun Kim
    •  & Hye Young Kim

  • Article
    | Open Access

    Invariant natural killer T (iNKT) cells are tissue-resident immune cells recognizing lipid antigens. Here the authors find that liver, but not lung nor spleen, iNKT cells alter their transcriptome upon systemic treatment of lipid nanoparticles for the induction of regulatory B cells and suppression of liver and pancreas autoimmunity in mouse models.

    • Channakeshava Sokke Umeshappa
    • , Patricia Solé
    •  & Pere Santamaria

  • 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

    Genetic alteration can render tumor cells resistant to immune cell-mediated killing. Here based on a genome-wide CRISPR screening, the authors show that expression of CHMP2A confers tumor cell resistance to NK cell-mediated cytotoxicity, mechanistically involving CHMP2A-dependent regulation of extracellular vesicle secretion.

    • Davide Bernareggi
    • , Qi Xie
    •  & Dan S. Kaufman

  • Article
    | Open Access

    Altered gut microbiome and exacerbation of symptoms at times of psychological stress are feature characteristics of Crohn’s disease. Here authors show in a mouse model that psychological stress impairs IL-22-dependent protective immunity of the ileal mucosa, which allows invasive bacteria to colonise the gut.

    • Christopher R. Shaler
    • , Alexandra A. Parco
    •  & Brian K. Coombes

  • Article
    | Open Access

    Phenotypic markers that overlap between ILC1 and NK populations have impacted the robust and specific analysis of these immune cell populations. Employing scRNA sequencing here the authors identify CD127+ CD94+ innate lymphoid cells that express granulysin and perforin and are expanded in patients with Crohn’s disease.

    • L. Krabbendam
    • , B. A. Heesters
    •  & H. Spits

  • 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

    Metabolic alterations control the fate and function of immune cells in response to infections, but the function of NK cell metabolism in the context of acute viral infections is unclear. Here the authors show that acute NK cell responses to Friend retrovirus involve increased glycolysis and mitochondrial metabolism and require amino acid transport as well as iron sufficiency.

    • Elisabeth Littwitz-Salomon
    • , Diana Moreira
    •  & David K. Finlay

  • Article
    | Open Access

    Mucosal-associated invariant T (MAIT) cells facilitate anti-microbial responses, but their functions in cancer protection is unclear. Here the authors show that activated MAIT cells induce an IFN-γ transcriptome in natural killer (NK) cells and enhance NK-dependent anti-cancer immunity in mice, thereby hinting a new avenue for cancer therapy.

    • Emma V. Petley
    • , Hui-Fern Koay
    •  & Phillip K. Darcy

  • Article
    | Open Access

    During wound healing and infection in the skin there is a hypoxic environment involving HIF-1α and NK cells. Here the authors show that NK cells through HIF-1α provide a cross-regulatory balance to provide an adequate antimicrobial defence that can inhibit subsequent wound healing.

    • Michal Sobecki
    • , Ewelina Krzywinska
    •  & Christian Stockmann

  • Article
    | Open Access

    Group 2 innate lymphoid cells (ILC2s) are a component of type 2 immune response recently described to be involved in the regulation of anti-tumor immune responses. Here, the authors show that the expression of the peroxisome proliferator-activated receptor γ (PPAPγ) in human and mouse ILC2 sustains type-2 cytokines secretion and support their pro-tumorigenic role in preclinical cancer models.

    • Giuseppe Ercolano
    • , Alejandra Gomez-Cadena
    •  & Camilla Jandus

  • Article
    | Open Access

    The role of the CD200–CD200R axis in regulating pulmonary inflammation is not completely understood. Here the authors show CD200R is expressed on type 2 innate lymphoid cells (ILC2s), and its engagement by CD200 ameliorates airway hyperreactivity and allergic asthma via inhibition of NF-κB signaling.

    • Pedram Shafiei-Jahani
    • , Doumet Georges Helou
    •  & Omid Akbari

  • Article
    | Open Access

    Innate lymphoid cells (ILCs) are important regulators of biological processes. Here the authors combine multiplexed imaging and computational pipelines to reveal tonsillar IRF4+ ILC3s, and to identify conserved stromal landmarks for ILC localization, thereby providing a platform for future ILC studies.

    • Anna Pascual-Reguant
    • , Ralf Köhler
    •  & Anja E. Hauser

  • Article
    | Open Access

    Necrotizing Enterocolitis (NEC) is an untreatable intestinal disease in infants. Here the authors show that human and experimental mouse NEC is associated with altered toll-like receptor expression in the intestine, enhanced Th17/type 3 polarization in adaptive immune and innate lymphoid cells, dysregulated microbiota, and reduced interleukin-37 signaling.

    • Steven X. Cho
    • , Ina Rudloff
    •  & Marcel F. Nold

  • Article
    | Open Access

    Group 2 innate lymphoid cells (ILC2s) are immune cells present in adipose tissue that contribute to metabolic homeostasis. Here the authors show that Death Receptor 3 (DR3) engagement on ILC2s ameliorates glucose tolerance, protects against insulin-resistance onset and reverses established insulin-resistance.

    • Pedram Shafiei-Jahani
    • , Benjamin P. Hurrell
    •  & Omid Akbari

  • 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

    Type 3 innate lymphoid cells (ILC3) are involved in maintaining gut immune homeostasis. Here the authors identify a circular RNA, circKcnt2, to be induced in ILC3s from inflamed gut, yet circKcnt2 deletion aggravates mouse experimental colitis, thereby implicating circKcnt2 as a potential feedback regulator of ILC3 activation and gut immunity.

    • Benyu Liu
    • , Buqing Ye
    •  & Zusen Fan

  • Article
    | Open Access

    PD-1 is a checkpoint inhibitory immune receptor that restrains proliferation and effector functions of a variety of cells, including ILC2s. Here the authors present a human PD-1 agonist that limits ILC2-dependent allergic airway disease in humanized mice and provide evidence that PD-1 signaling alters ILC2 function by modulation of cell metabolism.

    • Doumet Georges Helou
    • , Pedram Shafiei-Jahani
    •  & Omid Akbari

  • Article
    | Open Access

    Murine ILCs can modulate T cell responses in MHCII-dependent manner. Here the authors show that human ILCs process and present antigens and induce T-cell responses upon exposure to IL-1-family cytokines; along with the article by Lehmann et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

    • Anna Rao
    • , Otto Strauss
    •  & Jenny Mjösberg

  • Article
    | Open Access

    Group 3 innate lymphoid cells (ILC3s) promote T cell activation in the spleen but suppress it in the gut. Here, the authors show that this distinct regulation is mediated by gut microbiota-induced IL-23 and IFN-γ, respectively, and, along with the article by Rao et al, this work elucidates how cytokines set context specificity of ILC-T cell crosstalk by regulating ILC antigen presentation.

    • Frank Michael Lehmann
    • , Nicole von Burg
    •  & Daniela Finke

  • Article
    | Open Access

    Innate lymphoid cells (ILC) are important immune cells for maintaining the gut homeostasis. Here the authors show that c-FLIP, an anti-apoptotic molecule, is important for the development of NKP46+ ILC1, including conventional natural killer (cNK) cells, and ILC3, with cNK being more critical for ameliorating intestinal inflammation.

    • Ute Bank
    • , Katrin Deiser
    •  & Thomas Schüler

  • Article
    | Open Access

    As an interface between maternal and fetal tissues, decidua hosts immune cells specialized in fostering a successful pregnancy. Here the authors carry out high-dimensional characterization of function, morphology and surface markers of human decidual innate lymphoid cells (ILCs), identifying subsets with features distinct from blood ILC.

    • Oisín Huhn
    • , Martin A. Ivarsson
    •  & Francesco Colucci

  • Article
    | Open Access

    TGF-β is thought to be important for group 2 innate lymphoid cell (ILC2) function. Here the authors show that TGF-β drives expression of ST2 specifically in ILC2 progenitors and thereby is also important for the development of ILC2s in the bone marrow.

    • Li Wang
    • , Jun Tang
    •  & WanJun Chen

  • Article
    | Open Access

    Natural killer (NK) cells are important innate immune cells with diverse functions. Here the authors use single-cell RNA-sequencing of purified human bone marrow and peripheral blood NK cells to define five populations of NK cells with distinct transcriptomic profile to further our understanding of NK development and heterogeneity.

    • Chao Yang
    • , Jason R. Siebert
    •  & Subramaniam Malarkannan

  • Article
    | Open Access

    Here, Zimmer et al. analyze the natural killer (NK) cell response in a patient cohort with acute dengue virus infection showing early NK cell activation and proliferation, and the data suggest that NK cell proliferation depends on IL-18 signaling, and that responding NK cells have a skin-homing phenotype.

    • Christine L. Zimmer
    • , Martin Cornillet
    •  & Niklas K. Björkström

  • Article
    | Open Access

    Group 3 innate lymphoid cells (ILC3s) have important functions in inflammatory bowel disease. Here, the authors show that TL1A/DR3 signalling stimulates ILC3s to produce GM-CSF, thereby recruiting inflammatory cells, which results in subsequent IL-23-dependent loss of ILC3s and further intestinal inflammation.

    • Jingyu Li
    • , Wenli Shi
    •  & Ju Qiu

  • Article
    | Open Access

    Here, Frisbee et al. show that hypervirulent Clostridium difficile induces IL-33 expression in the gut and IL-33 reduces mortality and morbidity via group 2 innate lymphoid cells. Furthermore, serum levels of the soluble IL-33 decoy receptor, sST2, are associated with enhanced disease severity in human C. difficile patients.

    • Alyse L. Frisbee
    • , Mahmoud M. Saleh
    •  & William A. Petri Jr.

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