Interleukins articles within Nature Communications

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  • 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

    Our understanding of the immune response to SARS-CoV-2 infection is still incomplete. Here, the authors find that IL-33, produced during immune recall potentially by CD14+ monocytes, correlates with CD4+ T cell activation, anti-SARS-CoV-2 antibody titer, and disease severity in a cohort of convalescent individuals professionally exposed to the virus.

    • Michal A. Stanczak
    • , David E. Sanin
    •  & Erika L. Pearce

  • Article
    | Open Access

    Mucosal-associated invariant T (MAIT) cells are key in immunity and diseases, but how their effector polarization is controlled is still unclear. Here, the authors show that an IL-1β/IL-23/mTORC2 axis is essential for the induction of IL-17-producing MAIT17, while an IL-2/IL-15/mTORC1 axis is important for the homeostasis of IFN-γ-producing MAIT1.

    • Huishan Tao
    • , Yun Pan
    •  & Xiao-Ping Zhong

  • Article
    | Open Access

    Regulatory B (Breg) cells suppress excessive inflammation primary via the production of interleukin 10 (IL-10). Here the authors show that the function and homeostasis of mouse and human IL-10+ Breg cells are negatively regulated by the cell surface receptor, SLAMF5, to impact experimental autoimmunity, thereby hinting SLAMF5 as a potential target for immunotherapy.

    • Lihi Radomir
    • , Matthias P. Kramer
    •  & Idit Shachar

  • Article
    | Open Access

    Neutrophils secrete numerous immune effector molecules including cathelicidin which is associated with antimicrobial properties. Here the authors implicate neutrophil derived cathelicidin in modulation of CD4 T cell homoeostasis and the promotion of Th17 CD4 T cells.

    • Danielle Minns
    • , Katie J. Smith
    •  & Emily Gwyer Findlay

  • Article
    | Open Access

    Dynamic regulation of colonic secretory cell numbers is a critical component of the response to intestinal injury and inflammation. Here, the authors show that loss of the intracellular signalling regulator Sprouty2 in the intestinal epithelial cells is a protective response to injury that leads to increased secretory cell numbers, thus limiting colitis severity.

    • Michael A. Schumacher
    • , Jonathan J. Hsieh
    •  & Mark R. Frey

  • Article
    | Open Access

    Glioblastoma multiform (GBM) is a common and aggressive type of primary brain cancer that currently has no effective therapy. Here, the authors show, using a mouse GBM model and EGFRvIII-targeting chimeric antigen receptor (CAR)-T cells, that Intratumoral injection of interleukin-12 helps condition the microenvironment and promote anti-tumor immunity.

    • Giulia Agliardi
    • , Anna Rita Liuzzi
    •  & Burkhard Becher

  • Article
    | Open Access

    The WD40 domain of ATG16L1 is thought to be involved in non-canonical autophagy. Here the authors screen peptide libraries and identify interactions between this domain and the IL-2Rγ and IL-10RB receptors, indicating endosomal regulation of cytokine signalling by non-canonical autophagy.

    • Inmaculada Serramito-Gómez
    • , Emilio Boada-Romero
    •  & Felipe X. Pimentel-Muiños

  • Article
    | Open Access

    Hormonal contraception may alter women’s susceptibility to HIV. Here, the authors report the results of a randomized clinical trial substudy assessing the effects of injectable Net-En, oral contraceptives (COC) and Nuvaring on vaginal microbiota and cytokines, associating COC with lower microbial diversity and Nuvaring with increased inflammation.

    • Christina Balle
    • , Iyaloo N. Konstantinus
    •  & Heather B. Jaspan

  • Article
    | Open Access

    BATF is a transcription factor that is needed for IL-9 production by T helper 9 cells. Here the authors show that STAT5 is needed at the Il9 locus to enable BATF to function in this manner and that this interaction can reprogram other T helper subsets into IL-9 producing cells, thus regulating the immune response to disease.

    • Yongyao Fu
    • , Jocelyn Wang
    •  & Mark H. Kaplan

  • Article
    | Open Access

    Signaling of IL-33 via its receptor, ST2, has been implicated in macrophage function in tissue repair. Here the authors show, using genetic mouse models and single-cell transcriptomic data, that the IL-33/ST2 axis regulates both ILC2-derived IL-13 and macrophage differentiation/reparative function required for club cell regeneration.

    • Rania Dagher
    • , Alan M. Copenhaver
    •  & Marina Pretolani

  • Article
    | Open Access

    The pro-inflammatory cytokine IL-20 promotes tumor growth in several cancer types. Here, the authors show that high levels of IL-20 are associated with poor survival in patients with pancreatic ductal adenocarcinoma (PDAC) and that IL-20 blockade reduces tumor growth and alleviates cachexia symptoms in mouse models of PDAC.

    • Shao-Wei Lu
    • , Hong-Chin Pan
    •  & Ming-Shi Chang

  • Article
    | Open Access

    Intestinal IL-22 has important regulatory effects on the barrier and intestinal diseases and its production is controlled by the intestinal microbiome. Here the authors show that intestinal immune cell production of IL-22 is regulated by short chain fatty acids via an aryl hydrocarbon receptor and HIF1α-mediated mechanism that protects mice from intestinal inflammation.

    • Wenjing Yang
    • , Tianming Yu
    •  & Yingzi Cong

  • Article
    | Open Access

    Control over T. gondii infection in the brain involves microglial cells, but how these cells execute this control is not clear. Here the authors show that unlike IL-1β dominant macrophages, microglia are primed for gasdermin-D-dependent IL-1α production that is critical for protection against T. gondii infection.

    • Samantha J. Batista
    • , Katherine M. Still
    •  & Tajie H. Harris

  • Article
    | Open Access

    Type I IFN has apposing effects in neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS). Here the authors perform molecular profiling of NMOSD patients and mouse mechanistic experiments of neuro-inflammation to show that IFN-I stimulates pathogenic Th17 via IL-6 production by B cells.

    • Agnieshka M. Agasing
    • , Qi Wu
    •  & Robert C. Axtell

  • Article
    | Open Access

    Macrophages undergo a Warburg-like switch from oxidative phosphorylation to glycolysis in response to inflammatory stimulus. Here the authors show that fungal melanin can trigger this switch in human macrophages by sequestering calcium in the phagosome and enabling protection against Aspergillus fumigatus infection.

    • Samuel M. Gonçalves
    • , Cláudio Duarte-Oliveira
    •  & Agostinho Carvalho

  • Article
    | Open Access

    In macrophages, IL-1β secretion is mediated by N-GSDMD pores in the plasma membrane (PM). Here the authors show that in neutrophils, IL-1β secretion occurs in the absence of PM pores, via autophagosomes; N-GSDMD does not traffic to PM but to azurophilic granules, thereby releasing neutrophil elastase which cleaves further N-GSDMD into alternative fragments.

    • Mausita Karmakar
    • , Martin Minns
    •  & Eric Pearlman

  • 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

    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
    •  & Jannie Borst

  • Article
    | Open Access

    Immune cells contribute to the aortic wall destruction during abdominal aortic aneurysm (AAA) development. Here, Peshkova et al. show that cytokine signaling through interleukin-27 receptor is required for Angiotensin II-induced myelopoiesis and mature myeloid cells production, thus contributing to their aortic accumulation and aneurysm progression

    • Iuliia O. Peshkova
    • , Turan Aghayev
    •  & Ekaterina K. Koltsova

  • 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
    •  & Jane A. Skok

  • 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
    •  & Benjamin P. Fairfax

  • 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
    •  & Glaucia C. Furtado

  • Article
    | Open Access

    IL-36α,β and ɣ are IL-1-related cytokines promoting inflammation in the skin and intestine. Here the authors show they are elevated in individuals with obesity, and that mice lacking the IL-36 receptor antagonist are more resistant to diet-induced obesity and metabolic dysfunction, which depends on intestinal microbiota.

    • Eirini Giannoudaki
    • , Yasmina E. Hernandez-Santana
    •  & Patrick T. Walsh

  • 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

    Mast cells within the tumor microenvironment have controversial roles. Here, the authors show, using genetic mouse models, that in gastric cancer, mast cells at the periphery of the tumors are activated via cancer cell produced-IL33 and promote tumorigenesis by recruiting macrophages within the tumors.

    • Moritz F. Eissmann
    • , Christine Dijkstra
    •  & Matthias Ernst

  • Article
    | Open Access

    The inflammasomes are important mediators of protective immunity by promoting inflammatory cytokine production and cell death. Here the authors show that a lncRNA, Neat1, is mobilized by inflammasome-activating signals to promote the assembly of several inflammasome complexes and cytokine maturation to regulate inflammation.

    • Pengfei Zhang
    • , Limian Cao
    •  & Mian Wu

  • Article
    | Open Access

    The phosphatase Shp-2 was implicated in NK cell education due to its reported association with inhibitory receptors, but its function in this context is unclear. Here the authors show that Shp-2 is not required for NK cell function, but is necessary for IL-15-induced metabolic burst and expansion.

    • Charlène Niogret
    • , S. M. Shahjahan Miah
    •  & Greta Guarda

  • Article
    | Open Access

    CD4+ helper T cells producing IL-9 (Th9) have been implicated in anti-tumor immunity, with Th9 differentiation inducible in vitro via IL-4 and TGFβ treatment. Here the authors show that replacing TGFβ with IL-1β induces a distinct IL-9+ CD4+ population that have strong cytotoxic and anti-tumor activity in preclinical mouse models.

    • Gang Xue
    • , Guangxu Jin
    •  & Yong Lu

  • Article
    | Open Access

    Interleukin-2 (IL-2) signaling is required for regulatory T (Treg) cell differentiation in the thymus, but its function in peripheral Tregs is still unclear. Here the authors show, using inducible deletion of IL-2 receptor subunit CD25, that IL-2 signaling is essential for maintaining peripheral Treg homeostasis, but dispensable for lineage stability.

    • Kevin H. Toomer
    • , Jen Bon Lui
    •  & Thomas R. Malek

  • Article
    | Open Access

    Microfold cells (M-cell) are specialized cells of the intestine that sample luminal microbiota and dietary antigens. Here the authors show that epithelial non-canonical NFκB signalling, as induced by NIK, is important for M-cells maintenance, yet constitutive NIK activation is associated with gut inflammation and inflammatory bowel disease.

    • Sadeesh K. Ramakrishnan
    • , Huabing Zhang
    •  & Yatrik M. Shah

  • Article
    | Open Access

    Metabolic pathways are increasingly recognized as crucial determinants of T cell function. Here the authors show that the balance between IFNγ and IL-10 production in human CD4 T cells is modulated by the cholesterol biosynthetic pathway.

    • Esperanza Perucha
    • , Rossella Melchiotti
    •  & Andrew P. Cope

  • Article
    | Open Access

    Natural killer cells may respond better on second antigen encounters, but how this memory is induced or maintained in vivo is not clear. Here the authors show that memory NK cells expressing interleukin-7 (IL-7) receptor are induced in the lymph nodes but later recruited to liver for long term, IL-7 dependent survival and memory maintenance.

    • Xianwei Wang
    • , Hui Peng
    •  & Zhigang Tian

  • Article
    | Open Access

    Interleukin-9 (IL-9) is important for allergy, autoimmunity and tumor immunity, but how its expression is regulated is unclear. Here the authors show the essential function of an enhancer, CNS-25 in mouse and CNS-18 in human, for IL-9 expression, with the deletion of this enhancer severely hampering IL-9 production in mice or human cells.

    • Byunghee Koh
    • , Amina Abdul Qayum
    •  & Mark H. Kaplan

  • Article
    | Open Access

    Chronic inflammation often involves reactivation of memory adaptive immune. Here the authors show, using non-human primate models, that a single dose of anti-IL-7 receptor monoclonal antibody that exhibits antagonist but not agonist properties can reduce the frequency of antigen-specific T cell to help repress chronic skin inflammation.

    • Lyssia Belarif
    • , Caroline Mary
    •  & Nicolas Poirier

  • Article
    | Open Access

    T helper 2 (Th2) cells and type 2 innate lymphoid cells (ILC2) respond differently to interleukin-33 (IL-33) stimulation. Here the authors show that a phosphatase, Dusp10, is expressed in Th2, but not ILC2, to dephosphorylate p38 kinase, reduce GATA3 transcription factor activity, and suppress the induction of IL-5 in response to IL-33.

    • Takeshi Yamamoto
    • , Yusuke Endo
    •  & Toshinori Nakayama

  • Article
    | Open Access

    The inflammasome is normally activated by pathogens to induce tissue inflammation. Here the authors show that, in mouse experimental colitis models, Nlrp1 inflammasome sensor activates IL-18 to reduce beneficial colonic Clostridiales species, thereby decreasing microbial butyrate and its protective effects on colitis.

    • Hazel Tye
    • , Chien-Hsiung Yu
    •  & Seth L. Masters

  • Article
    | Open Access

    IL-1β in gingival crevicular fluid (GCF) is a marker of inflammation in periodontal disease. Here, Offenbacher et al. identify genetic variants in the IL37 locus associated with GCF-IL-1β and show that the IL-1β-increasing allele at rs3811046 leads to an enhanced inflammatory response in vitro and in vivo.

    • Steven Offenbacher
    • , Yizu Jiao
    •  & Kari E. North

  • Article
    | Open Access

    Cytokines such as TNF and IFN-γ are important for immunity against hepatitis B virus (HBV). Here the authors show that interleukin-32 gamma (IL-32γ) acts downstream of TNF and IFN-γ as an intracellular effector, and that IL-32γ negatively regulates host factors contributing to HBV transcription to promote HBV clearance.

    • Doo Hyun Kim
    • , Eun-Sook Park
    •  & Kyun-Hwan Kim

  • Article
    | Open Access

    Interleukin-33 (IL-33) can be released as a cytokine or transported into the nucleus, but the significance of this nuclear shuttling is not fully understood. Here the authors show that chromatin-binding of IL-33 alters, unexpectedly, the activity of IL-33 both in alarmin release kinetics and receptor signaling capacity.

    • Jared Travers
    • , Mark Rochman
    •  & Marc E. Rothenberg

  • Article
    | Open Access

    Interleukin-15 (IL-15) regulates the homeostasis of many immune cell types, including natural killer T (NKT) cells, but the underlying mechanism is not completely clear. Here the authors analyse Tbkbp1-deficient mice and show that IL-15 induces Tbkbp1-dependent autophagy to modulate NKT survival.

    • Lele Zhu
    • , Xiaoping Xie
    •  & Shao-Cong Sun

  • Article
    | Open Access

    Glutamine can feed into the TCA cycle as a fuel for oxidative phosphorylation and thereby can affect metabolic pathways in lymphocytes. Yet here the authors show that glutamine serves predominantly as a signalling molecule that sustains cMyc expression to control NK cell metabolism and effector function.

    • Róisín M. Loftus
    • , Nadine Assmann
    •  & David K. Finlay

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