Journal ArticleDOI
IL-33 is more potent than IL-25 in provoking IL-13–producing nuocytes (type 2 innate lymphoid cells) and airway contraction
Jillian L. Barlow,Samantha Peel,Jane Fox,Veera Panova,Clare S. Hardman,Ana Camelo,Christine Bucks,Xiaoying Wu,Colleen M. Kane,Daniel R. Neill,Robin J. Flynn,Ian Sayers,Ian P. Hall,Andrew N. J. McKenzie +13 more
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TLDR
This paper showed that IL-33 plays a critical role in the rapid induction of airway contraction by stimulating the prompt expansion of IL-13-producing type 2 innate lymphoid cells, whereas IL-25 induced responses are slower and less potent.Abstract:
Background IL-25 and IL-33 belong to distinct cytokine families, but experimental mouse studies suggest their immunologic functions in type 2 immunity are almost entirely overlapping. However, only polymorphisms in the IL-33 pathway ( IL1RL1 and IL33 ) have been significantly associated with asthma in large-cohort genome-wide association studies. Objective We sought to identify distinct pathways for IL-25 and IL-33 in the lung that might provide insight into their roles in asthma pathogenesis and potential for therapeutic intervention. Methods IL-25 receptor–deficient (Il17rb −/− ) , IL-33 receptor–deficient (ST2, Il1rl1 −/− ), and double-deficient (Il17rb −/− Il1rl1 −/− ) mice were analyzed in models of allergic asthma. Microarrays, an ex vivo lung slice airway contraction model, and Il13 +/eGFP mice were then used to identify specific effects of IL-25 and IL-33 administration. Results Comparison of IL-25 and IL-33 pathway–deficient mice demonstrates that IL-33 signaling plays a more important in vivo role in airways hyperreactivity than IL-25. Furthermore, methacholine-induced airway contraction ex vivo increases after treatment with IL-33 but not IL-25. This is dependent on expression of the IL-33 receptor and type 2 cytokines. Confocal studies with Il13 +/eGFP mice show that IL-33 more potently induces expansion of IL-13–producing type 2 innate lymphoid cells, correlating with airway contraction. This predominance of IL-33 activity is enforced in vivo because IL-33 is more rapidly expressed and released in comparison with IL-25. Conclusion Our data demonstrate that IL-33 plays a critical role in the rapid induction of airway contraction by stimulating the prompt expansion of IL-13–producing type 2 innate lymphoid cells, whereas IL-25–induced responses are slower and less potent.read more
Citations
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Journal ArticleDOI
Interleukin-33 in health and disease
TL;DR: The molecular and cellular characteristics of IL-33 are highlighted, together with its major role in health and disease and the potential therapeutic implications of these findings in humans are highlighted.
Journal ArticleDOI
IL-33: an alarmin cytokine with crucial roles in innate immunity, inflammation and allergy.
TL;DR: The cellular sources, mode of action and regulation of IL-33 are discussed, and its crucial roles in vivo are highlighted with particular emphasis on results obtained using IL33-deficient mice.
Journal ArticleDOI
Interleukin-33 (IL-33): A nuclear cytokine from the IL-1 family
TL;DR: 15 years of discoveries on IL‐33 protein are highlighted, including its molecular characteristics, nuclear localization, bioactive forms, cellular sources, mechanisms of release and regulation by proteases, and important roles in allergic, fibrotic, infectious, and chronic inflammatory diseases.
Journal ArticleDOI
The ST2/IL-33 Axis in Immune Cells during Inflammatory Diseases
Brad Griesenauer,Sophie Paczesny +1 more
TL;DR: Recently, sST2 has been shown to be secreted by intestinal pro-inflammatory T cells during gut inflammation; on the contrary, protective ST2-expressing Tregs are decreased, implicating that ST2/IL-33 signaling may play an important role in intestinal disease.
Journal ArticleDOI
Innate Lymphoid Cells in Inflammation and Immunity
TL;DR: A new role for ILCs in the maintenance of metabolic homeostasis has started to emerge, underlining their importance in fundamental physiological processes beyond infection and immunity.
References
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Journal ArticleDOI
IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines
Jochen Schmitz,Alexander Owyang,Elizabeth R. Oldham,Yaoli Song,Erin Murphy,Terril K. McClanahan,Gerard Zurawski,Mehrdad M. Moshrefi,Jinzhong Qin,Xiaoxia Li,Daniel M. Gorman,J. Fernando Bazan,Robert A. Kastelein +12 more
TL;DR: A member of theIL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T( H)2 cells is reported.
Journal ArticleDOI
RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement
Yoichi Shinkai,Gary Rathbun,Kong-Peng Lam,E. M. Oltz,Valerie Stewart,Monica Mendelsohn,Jean Charron,Milton Datta,Faith Young,Alan M. Stall,Frederick W. Alt +10 more
TL;DR: Loss of RAG-2 function in vivo results in total inability to initiate V(D)J rearrangement, leading to a novel severe combined immune deficient (SCID) phenotype.
Journal ArticleDOI
Requirement for IL-13 Independently of IL-4 in Experimental Asthma
Gabriele Grünig,Martha L. Warnock,Adil E. Wakil,Rajeev Venkayya,Frank Brombacher,Donna M. Rennick,Dean Sheppard,Markus Mohrs,Debra D. Donaldson,Richard M. Locksley,David B. Corry +10 more
TL;DR: This article showed that IL-4 receptor α chain-dependent pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL4 receptor and showed that selective neutralization of IL-13, a cytokine related to interleukin-4 that also binds to the α chain of the IL 4 receptor, ameliorated asthma phenotype.
Journal ArticleDOI
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity
Daniel R. Neill,See Heng Wong,Agustin Bellosi,Robin J. Flynn,Maria Daly,Theresa K. A. Langford,Christine Bucks,Colleen M. Kane,Padraic G. Fallon,Richard Pannell,Helen E. Jolin,Andrew N.J. McKenzie +11 more
TL;DR: The identification and functional characterization of a new innate type-2 immune effector leukocyte that is named the nuocyte is presented, which represents a critically important innate effector cell in type- 2 immunity.
Journal ArticleDOI
A large-scale, consortium-based genomewide association study of asthma.
Miriam F. Moffatt,Ivo Gut,Florence Demenais,David P. Strachan,Emmanuelle Bouzigon,Simon Heath,Erika von Mutius,Martin Farrall,Mark Lathrop,William O.C.M. Cookson +9 more
TL;DR: A few common alleles are associated with disease risk at all ages and suggest a role for communication of epithelial damage to the adaptive immune system and activation of airway inflammation in asthma.
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