Cytokines

  • Article
    | Open Access

    Infections induce activation of naïve T cells for protective immunity, but insights for this host-pathogen crosstalk are still missing. Here the authors show that infection-induced type I interferon (IFN-I) signaling promote the differentiation, expansion and functional maturation of naïve CD8 T cells, particularly for low affinity clones, to enhance anti-microbial immunity.

    • Mladen Jergović
    • , Christopher P. Coplen
    •  & Janko Nikolich-Žugich
  • Article
    | Open Access

    Interferon (IFN) is an important component of antiviral immunity, but can also be exploited by bacteria for immune evasion. Here the authors show that Listeria monocytogenes (Lm) induces type I IFN to suppress the degradation of Lm virulence proteins, ActA and LLO, and promote Lm infection in an IFITM3-dependent manner, thereby hinting at a potential target for antimicrobial therapy.

    • Joel M. J. Tan
    • , Monica E. Garner
    •  & John H. Brumell
  • Article
    | Open Access

    The authors profile stool metagenomics and plasma metabolomics in Tanzanian individuals and uncover a gradient of gut microbial profiles, from rural through urban Tanzania towards Western populations. Integration with ex vivo blood microbial stimulations reveals immune responses associated with histidine and arginine pathways, mediated by Bifidobacterium longum and Akkermansia muciniphila.

    • Martin Stražar
    • , Godfrey S. Temba
    •  & Ramnik J. Xavier
  • Article
    | Open Access

    Intraepithelial lymphocytes (IEL) respond to IL-15 complexed with IL-15Ra but how this intrinsically affects IEL is unclear. Here the authors use proteomics analyses of the main mouse IEL subsets and identify PIM kinases as essential for IEL proliferation, metabolism and effector function downstream of IL-15.

    • Olivia J. James
    • , Maud Vandereyken
    •  & Mahima Swamy
  • Article
    | Open Access

    Our ability to interpret single-cell multivariate signaling responses is still limited. Here the authors introduce fractional response analysis (FRA), involving fractional cell counting, capable of deconvoluting heterogeneous multivariate responses of cellular populations.

    • Karol Nienałtowski
    • , Rachel E. Rigby
    •  & Michał Komorowski
  • Article
    | Open Access

    Cancer derived exosomes are reported to promote metastatic dissemination. Here the authors show that cytokines in the tumor microenvironment bind to exosomes via glycosaminoglycan side chains of proteoglycans, and these exosomes are preferentially taken up by specific cell lineages and organs to promote metastasis.

    • Luize G. Lima
    • , Sunyoung Ham
    •  & Andreas Möller
  • Article
    | Open Access

    Some patients with COVID-19 fail to clear the viral infection quickly, yet our understanding for the underlying immune characteristics is still lacking. Here the authors use single-cell RNA sequencing and other data form such patients to show that persistent infection is associated with immune suppression and reduced expression of ribosomal protein genes.

    • Bin Yang
    • , Junpeng Fan
    •  & Chaoyang Sun
  • Article
    | Open Access

    Lung resident memory T (TRM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung TRM cells that might be important to limit reinfection.

    • Judith Grau-Expósito
    • , Nerea Sánchez-Gaona
    •  & Meritxell Genescà
  • Article
    | Open Access

    Controlled cell death can be an efficient anti-viral strategy, but also leads to tissue damage and needs to be balanced. Oyler-Yaniv et al. combine mathematical modelling and microscopy to show that exposure to TNF in response to viral infection causes cells to tune their speed-vs-accuracy trade-off in cell death decision to limit HSV-1 spread.

    • Jennifer Oyler-Yaniv
    • , Alon Oyler-Yaniv
    •  & Roy Wollman
  • Article
    | Open Access

    Interactions between the immune system and adipose tissue contribute to the regulation of body weight, however, the underlying mechanisms remain incompletely understood. Here the authors dissect the role of two structurally and functionally similar immune mediators, BAFF and APRIL, in modifying diet-induced weight gain and adipocyte lipid handling.

    • Calvin C. Chan
    • , Isaac T. W. Harley
    •  & Senad Divanovic
  • Article
    | Open Access

    Asthma is caused by hyperreactivity to benign antigens, with humoral immunity orchestrated by interleukin-4 (IL-4) and IL-13 being the key etiological factor. Here the authors show, in humanized mouse models, that dual vaccination against IL-4 and IL-13 induces their durable suppression ameliorate experimental asthma, and to hint clinical translation.

    • Eva Conde
    • , Romain Bertrand
    •  & Laurent L. Reber
  • Article
    | Open Access

    Despite being prevalent yet well studied, ulcerative colitis still has poorly characterized pathophysiology. Here the authors use mouse colitis models to find that type I and III interferon (IFN) both contribute to ameliorating the disease, with IFN signaling in either the epithelial or hematopoietic compartment sufficient for this protective effect.

    • Constance McElrath
    • , Vanessa Espinosa
    •  & Sergei V. Kotenko
  • 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

    Lupus pathogenesis is associated with high type 1 interferon stimulated gene (ISG) expression. Here, the authors correlate ISG expression in CD8+ T cells from lupus nephritis patients with abnormal mitochondrial function, implicating increased NAD consumption and reduced cell viability in the pathogenesis.

    • Norzawani Buang
    • , Lunnathaya Tapeng
    •  & Marina Botto
  • 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

    Metabolism changes can modulate immune responses in many contexts, and vice versa. Here the authors associate metabolomic, as well as cytokine and chemokine, data from stratified COVID-19 patients to find that arginine, tryptophan and purine metabolic pathways correlate with hyperproliferation, thus hinting at potential therapeutic targets for severe COVID-19 patients.

    • Nan Xiao
    • , Meng Nie
    •  & Zeping Hu
  • Article
    | Open Access

    NF-κB signalling is critical to TLR mediated cytokine release in various immune responses. Here the authors show how N4BP1 inhibits NEMO signalling and subsequent NF-κB activation and how this pathway is negatively regulated by caspase-8 cleavage of N4BP1.

    • Hexin Shi
    • , Lei Sun
    •  & Bruce Beutler
  • 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

    TNF can be inhibited by small molecules that stabilize the TNF trimer in an asymmetric conformation. Here, the authors develop a monoclonal antibody that selectively binds this inactive form of TNF, enabling both target engagement assessment and structural characterization of TNF binding to TNF receptor 1.

    • Daniel J. Lightwood
    • , Rebecca J. Munro
    •  & Alastair D. G. Lawson
  • Article
    | Open Access

    Small molecules stabilising a distorted TNF trimer can inhibit TNF signaling, but the underlying mechanism is unclear. Here, the authors characterize the inhibitor-bound TNF-receptor complex structurally and biochemically, showing that the inhibitors alter TNF-receptor binding stoichiometry and cluster formation.

    • David McMillan
    • , Carlos Martinez-Fleites
    •  & James O’Connell
  • 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

    Excessive interferon (IFN) responses often follow viral infection to induce pathology or even death. Here the authors show that a signaling adaptor, β-arrestin 2, enhances the cGAS/STING innate immunity signaling pathway to promote IFN-β production, but may be degraded in infected cells to serve as a target of viral immune evasion.

    • Yihua Zhang
    • , Manman Li
    •  & Dapeng Yan
  • Article
    | Open Access

    The development of specific anti-cytokine/chemokine therapeutic strategies for atherosclerotic disease is challenging. Here, the authors have designed a peptide-based ectodomain mimic of the chemokine receptor CXCR4 that selectively targets MIF but not CXCL12 and blocks experimental atherosclerosis in vivo.

    • Christos Kontos
    • , Omar El Bounkari
    •  & Jürgen Bernhagen
  • 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

    The human skin is a highly complex organ comprising multiple tissue layers and diverse cell types. Here, the authors present a spatially-resolved quantitative proteomic atlas of the healthy human skin, characterizing the protein profiles of four skin layers and nine cell types.

    • Beatrice Dyring-Andersen
    • , Marianne Bengtson Løvendorf
    •  & Matthias Mann
  • Article
    | Open Access

    GM-CSF is involved in control over M. tuberculosis infection. Here the authors show that GM-CSF reduces type 1 interferon driven neutrophil recruitment, NETosis and bacterial growth in the lungs of infected mice, and provide evidence that this NETosis occurs in infected humans who are not responsive to antibiotic therapy.

    • Lúcia Moreira-Teixeira
    • , Philippa J. Stimpson
    •  & Anne O’Garra
  • 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

    SOCS1 is a potent suppressor of JAK-STAT signalling responses to IFNγ and γ-chain cytokines and thereby limits inflammation. Here the authors identify and characterize heterozygous SOCS1 mutations in 10 patients from 5 unrelated families with autoimmune diseases.

    • Jérôme Hadjadj
    • , Carla Noemi Castro
    •  & Frédéric Rieux-Laucat
  • Article
    | Open Access

    COVID-19 severity is associated with cytokine levels and lymphopenia, but the role of immune cell subsets is not well understood. Here the authors immunophenotype whole blood samples from 54 COVID-19 patients and find that the immature neutrophil-to-VD2 T-cell ratio is associated with severe COVID-19.

    • Guillaume Carissimo
    • , Weili Xu
    •  & Lisa FP Ng
  • 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

    HMGB1 is an inflammatory mediator released by a variety of cell types. Here, the authors show that unlike IL-1β, HMGB1 is released non-specifically following cell lysis.

    • Allen Volchuk
    • , Anna Ye
    •  & Neil M. Goldenberg
  • Article
    | Open Access

    Anti-androgen therapy inhibits prostate cancer (PC) progression, and is thought to act directly on cancer cells. Here the authors show that androgen receptor is expressed on normal and PC-associated macrophages, and its stimulation alters macrophage secretome to promote migration of cultured PC cell lines.

    • Bianca Cioni
    • , Anniek Zaalberg
    •  & Andries M. Bergman
  • 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

    Macrophages survey their surroundings using macropinocytosis, but its regulation is unclear. Here, the authors report that SLIT2, a known inhibitor of Rac GTPases, is an endogenous inhibitor of macropinocytosis, and that SLIT2 limits the uptake of NOD2 ligands into immune cells and subsequent release of the inflammatory chemokine, CXCL1, in vivo.

    • Vikrant K. Bhosle
    • , Tapas Mukherjee
    •  & Lisa A. Robinson
  • Article
    | Open Access

    The pandemic of SARS-CoV-2 post a significant threat to public health. Here the authors show, by screening 23 viral proteins, that both structural and non-structural SARS-CoV-2 proteins are capable of modulating host innate immunity and type interferon responses, with this information serves to warrant further studies on SARS-CoV-2 pathogenesis.

    • Xiaobo Lei
    • , Xiaojing Dong
    •  & Jianwei Wang
  • 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

    Altered monocyte responses and testosterone levels correlate, individually, with the pathogenesis of hepatic amebiasis in mice. Here the authors show that testosterone induces enhanced TNF/CXCL1 expression and stronger proinflammatory responses in both human and mouse monocytes to support an androgen-monocyte axis of inflammation regulation.

    • Julie Sellau
    • , Marie Groneberg
    •  & Hannelore Lotter