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Orphan receptor IL-17RD regulates Toll-like receptor signalling via SEFIR/TIR interactions
Toll-like receptors detect conserved microbial features to initiate host defence and are tightly regulated. Here the authors show that the orphan receptor interleukin-17 receptor D negatively regulates signalling downstream of Toll-like receptors to prevent excessive inflammation.
- Mark Mellett
- , Paola Atzei
- & Paul N. Moynagh
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| Open AccessXanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation
Activation of NLRP3 inflammasome requires generation of reactive oxygen species. Here the authors show that microbial or tissue damage-derived signals activate xanthine oxidase, which serves as a critical source of reactive oxygen species for inflammasome activation in macrophages.
- Annette Ives
- , Johji Nomura
- & Alexander So
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A clonotypic Vγ4Jγ1/Vδ5Dδ2Jδ1 innate γδ T-cell population restricted to the CCR6+CD27− subset
Functional diversity of T cells expressing antigen receptors composed of γ and δ chains is just beginning to be appreciated. Here the authors show that within γδ T cells of highly diverse Vγ4+repertoire there is a population with germline rearranged, invariant TCR and a distinct phenotype.
- Elham Kashani
- , Lisa Föhse
- & Immo Prinz
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| Open AccessIL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology
Macrophages and dendritic cells contribute to gut homeostasis and mucosal immune defense. Here, Aychek et al. describe an IL-23-based crosstalk between these cells that prevents lethal immunopathology during Citrobacter rodentiuminfection.
- Tegest Aychek
- , Alexander Mildner
- & Steffen Jung
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IL-10 inhibits neuraminidase-activated TGF-β and facilitates Th1 phenotype during early phase of infection
The role of IL-10 in influenza infection is controversial. Here the authors show that early during infection, IL-10 promotes Th1 immunity by inhibiting viral neuraminidase-mediated release of TGF-β, but later acts as an immunosuppressive cytokine to inhibit immunopathology and promote recovery.
- Avijit Dutta
- , Ching-Tai Huang
- & Yueh-Chia He
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Mitochondrial Ca2+-dependent NLRP3 activation exacerbates the Pseudomonas aeruginosa-driven inflammatory response in cystic fibrosis
Airway epithelia from cystic fibrosis patients show an exaggerated inflammatory response to P. aeruginosa. Here, Rimessi et al. show that P. aeruginosa exposure causes augmented Ca2+signalling in the absence of functional CFTR, leading to mitochondrial damage and activation of the NLRP3 inflammasome.
- Alessandro Rimessi
- , Valentino Bezzerri
- & Paolo Pinton
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TH2 cells and their cytokines regulate formation and function of lymphatic vessels
Lymphatic vessels remodel in response to inflammatory conditions and T-cell-secreted cytokines. Here, the authors show that T helper type 2 cells inhibit lymphangiogenesis by secreting IL-4 and IL-13, and that blockade of these cytokines can alleviate allergic asthma symptoms by improving the lymphatic function in mice.
- Kihyuk Shin
- , Raghu P. Kataru
- & Seung-Hyo Lee
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Chromatin remodelling and autocrine TNFα are required for optimal interleukin-6 expression in activated human neutrophils
How IL-6 expression is regulated in human neutrophils has remained unclear. Here the authors show, using highly purified neutrophils, that TLR8 or TLR4 signalling activates latent enhancers and cooperates with autocrine TNFα to induce IL-6transcription.
- Maili Zimmermann
- , Francisco Bianchetto Aguilera
- & Marco A. Cassatella
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IL-10 engages macrophages to shift Th17 cytokine dependency and pathogenicity during T-cell-mediated colitis
The pro-inflammatory cytokine IL-1ß promotes the accumulation of pathologic Th17 lymphocytes that contribute to colitis. Here the authors show that the critical role of IL-10 in colitis suppression can be explained by its inhibition of IL-1ß production in macrophages.
- Bofeng Li
- , Prajwal Gurung
- & Terrence L. Geiger
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Identification of a subnuclear body involved in sequence-specific cytokine RNA processing
Processing of interleukin RNAs must be tightly controlled during the immune response. Here, the authors identify TDP-43 as a scaffold protein for the formation of a nuclear body that is important for interleukin RNA processing and stability.
- Sungwook Lee
- , Taeyun A. Lee
- & Boyoun Park
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| Open AccessThe structural basis for receptor recognition of human interleukin-18
IL-18 is a member of the IL-1 family of proinflammatory cytokines. Tsutsumi et al.present a crystal structure of IL-18 bound to the extracellular domains of its heterodimeric receptor, providing insight into how its unusual specificity may be targeted pharmacologically.
- Naotaka Tsutsumi
- , Takeshi Kimura
- & Zenichiro Kato
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Interleukin-1α released from HSV-1-infected keratinocytes acts as a functional alarmin in the skin
HSV-1 is known to evade the immune system by retention of interleukin-1β. Here, the authors show that HSV-1-infected keratinocytes circumvent this mechanism by release of interleukin-1α, which recruits leukocytes and prevents viral dissemination.
- Katelynn A. Milora
- , Samantha L. Miller
- & Liselotte E. Jensen
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IL-37 protects against obesity-induced inflammation and insulin resistance
Inflammation is a hallmark of obesity and driver of various associated pathologies. Here the authors show that mice overexpressing the anti-inflammatory cytokine IL-37 are protected from the metabolic consequences of a high-fat diet, and that plasma levels of IL-37 correlate with insulin sensitivity in humans.
- Dov B. Ballak
- , Janna A. van Diepen
- & Rinke Stienstra
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IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORγt
Negative selection of double-positive thymocytes that express autoreactive T-cell receptors plays a crucial role in the maintenance of self-tolerance. Here, the authors provide evidence that the cytokine IL-23 produced by thymic dendritic cells is involved in the depletion of double-positive thymocytes.
- Hao Li
- , Hui-Chen Hsu
- & John D. Mountz
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Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation
Skin-resident IL-17-producing γδT cells have an important role in skin inflammation but their development and trafficking is not well established. Here, Cai et al. unveil differences in the developmental requirements and functional regulation of two subsets of dermal γδT cells.
- Yihua Cai
- , Feng Xue
- & Jun Yan
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IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1
Autoimmune diseases are regulated by the balance between pro- and anti-inflammatory cytokines. Here, the authors show that the transcriptional regulator Blimp1 is induced in inflammatory T helper cells by the cytokines IL-27 and IL-12 to counteract pro-inflammatory IL-23 and promote resolution of tissue inflammation.
- Christina Heinemann
- , Sylvia Heink
- & Thomas Korn
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IL-21 induces IL-22 production in CD4+ T cells
The cytokine interleukin-22 maintains the integrity of the colonic epithelium during inflammation. Here, the authors show that IL-21 regulates the production of IL-22 in T cells and this mechanism plays a protective role in a mouse model of colitis.
- Ada Yeste
- , Ivan D. Mascanfroni
- & Francisco J Quintana
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FoxP3+ regulatory T cells promote influenza-specific Tfh responses by controlling IL-2 availability
Regulatory T cells (Tregs) are mainly known to suppress effector T cell and B-cell responses. Here, the authors demonstrate that Tregs are able to promote T follicular helper and germinal centre B-cell responses to influenza by sequestering IL-2, the negative regulator of T follicular helper cell differentiation.
- Beatriz León
- , John E. Bradley
- & André Ballesteros-Tato
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Crystal structures of interleukin 17A and its complex with IL-17 receptor A
Interleukin-17A homodimers preferentially interact with heterodimeric IL-17 receptors. By solving the crystal structure of an IL-17A homodimer in complex with a single IL-17RA receptor subunit, the authors reveal conformational changes in IL-17A that lead to exclusion of a second IL-17RA subunit.
- Shenping Liu
- , Xi Song
- & Matthew C. Griffor
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MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
Mice lacking the anti-inflammatory cytokine IL-10 can develop colitis, which depends on inappropriate responses to commensal bacteria. Hoshiet al. now show that these responses are driven by colonic mononuclear phagocytes, providing insight to the initiating events, which may underlie inflammatory bowel disease.
- Namiko Hoshi
- , Dominik Schenten
- & Ruslan Medzhitov
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Orphan receptor IL-17RD tunes IL-17A signalling and is required for neutrophilia
One of the five IL-17 receptors, IL-17RD lacks a motif thought to be required for downstream signalling. Melletet al. show that IL-17RD tunes IL-17A-dependent signalling; in its absence, MAPK signalling and neutrophil recruitment are impaired, but NF-κB activation is enhanced.
- Mark Mellett
- , Paola Atzei
- & Paul N. Moynagh
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| Open AccessFoxP3+ regulatory CD4 T cells control the generation of functional CD8 memory
The role of CD4+ T cells in the generation of memory CD8+ T cells is not fully understood. In this study, the exposure of CD8 memory precursors to interleukin-2 during early antigen priming is shown to be controlled by FoxP3+ regulatory CD4+T cells, resulting in the production of functional memory cells.
- M.G. de Goër de Herve
- , S. Jaafoura
- & Y. Taoufik
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Sensing of mammalian IL-17A regulates fungal adaptation and virulence
It is unclear whether pathogens can advantageously exploit the host's immune response. UsingCandida albicans, the authors show that host IL-17A binds to the fungi and induces nutrient starvation and autophagy, which eventually leads to enhanced biofilm formation and resistance to the hosts' defence.
- Teresa Zelante
- , Rossana G. Iannitti
- & Luigina Romani