A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis.
Maryam Salimi,Jillian L. Barlow,Sean P. Saunders,Luzheng Xue,Danuta Gutowska-Owsiak,Xinwen Wang,Li-Chieh Huang,David Johnson,Seth T. Scanlon,Andrew N. J. McKenzie,Padraic G. Fallon,Padraic G. Fallon,Graham S. Ogg +12 more
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TLDR
Type 2 innate lymphoid cells promote skin inflammation in mice and men, in part by producing IL-5 and IL-13 in response to IL-33.Abstract:
Type 2 innate lymphoid cells (ILC2s, nuocytes, NHC) require RORA and GATA3 for their development. We show that human ILC2s express skin homing receptors and infiltrate the skin after allergen challenge, where they produce the type 2 cytokines IL-5 and IL-13. Skin-derived ILC2s express the IL-33 receptor ST2, which is up-regulated during activation, and are enriched in lesional skin biopsies from atopic patients. Signaling via IL-33 induces type 2 cytokine and amphiregulin expression, and increases ILC2 migration. Furthermore, we demonstrate that E-cadherin ligation on human ILC2 dramatically inhibits IL-5 and IL-13 production. Interestingly, down-regulation of E-cadherin is characteristic of filaggrin insufficiency, a cardinal feature of atopic dermatitis (AD). ILC2 may contribute to increases in type 2 cytokine production in the absence of the suppressive E-cadherin ligation through this novel mechanism of barrier sensing. Using Rag1(-/-) and RORα-deficient mice, we confirm that ILC2s are present in mouse skin and promote AD-like inflammation. IL-25 and IL-33 are the predominant ILC2-inducing cytokines in this model. The presence of ILC2s in skin, and their production of type 2 cytokines in response to IL-33, identifies a role for ILC2s in the pathogenesis of cutaneous atopic disease.read more
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Control of adaptive immunity by the innate immune system
Akiko Iwasaki,Ruslan Medzhitov +1 more
TL;DR: These emerging principles of innate control of adaptive immunity are discussed, which are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set ofinflammatory cytokines, which in turn activate effector responses.
Journal ArticleDOI
The biology of innate lymphoid cells
David Artis,Hergen Spits +1 more
TL;DR: This work summarizes the studies that formally identified innate lymphoid cells and highlights their emerging roles in controlling tissue homeostasis in the context of infection, chronic inflammation, metabolic disease and cancer.
Journal ArticleDOI
Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis
Christoph S.N. Klose,David Artis +1 more
TL;DR: This Review highlights experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.
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.
References
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Journal ArticleDOI
Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis
Colin N. A. Palmer,Alan D. Irvine,Ana Terron-Kwiatkowski,Yiwei Zhao,Haihui Liao,Simon P. Lee,David Goudie,Aileen Sandilands,Linda E. Campbell,Frances J.D. Smith,Grainne M. O'Regan,Rosemarie Watson,Jo E Cecil,Sherri J. Bale,John G. Compton,John J. DiGiovanna,John J. DiGiovanna,Philip Fleckman,Sue Lewis-Jones,Gehan Arseculeratne,Ann Sergeant,Colin S. Munro,Brahim El Houate,Ken McElreavey,Liselotte Brydensholt Halkjaer,Hans Bisgaard,Somnath Mukhopadhyay,Somnath Mukhopadhyay,W.H. Irwin McLean +28 more
TL;DR: It is shown that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis.
Journal ArticleDOI
Innate lymphoid cells--a proposal for uniform nomenclature.
Hergen Spits,David Artis,Marco Colonna,Andreas Diefenbach,James P. Di Santo,Gérard Eberl,Shigeo Koyasu,Richard M. Locksley,Andrew N.J. McKenzie,Reina E. Mebius,Fiona Powrie,Eric Vivier,Eric Vivier +12 more
TL;DR: It is proposed that ILCs should be categorized into three groups based on the cytokines that they can produce and the transcription factors that regulate their development and function.
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
Innate production of T H 2 cytokines by adipose tissue-associated c-Kit + Sca-1 + lymphoid cells
Kazuyo Moro,Taketo Yamada,Masanobu Tanabe,Tsutomu Takeuchi,Tomokatsu Ikawa,Hiroshi Kawamoto,Jun Ichi Furusawa,Masashi Ohtani,Hideki Fujii,Shigeo Koyasu +9 more
TL;DR: In this article, a new type of innate lymphocyte present in a novel lymphoid structure associated with adipose tissues in the peritoneal cavity was reported. But these cells do not express lineage (Lin) markers but do express c-Kit, Sca-1 (also known as Ly6a), IL7R and IL33R.
Journal ArticleDOI
New insights into atopic dermatitis
TL;DR: This review summarizes recent progress in the understanding of the pathophysiology of atopic dermatitis and the implications for new management strategies.
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