A role for IL-25 and IL-33–driven type-2 innate lymphoid cells in atopic dermatitis

Salimi, Maryam; Barlow, Jillian L.; Saunders, Sean P.; Xue, Luzheng; Gutowska-Owsiak, Danuta; Wang, Xinwen; Huang, Li-Chieh; Johnson, D. S.; Scanlon, Seth Thomas; McKenzie, Andrew N. J.; Fallon, Padraic G.; Ogg, Graham S.

doi:10.1084/jem.20130351

Cited by 841 publications

(1,076 citation statements)

References 45 publications

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“…These data are consistent with the elevated IL33 mRNA reported previously in the lesional skin of patients with AD and, similarly, the detection of higher levels of IL-25 in patients with AD (46)(47)(48). Notably, IL-33, and to a lesser extent TSLP (but not IL-25), induced migration of skin-derived human ILC2 (45,49).…”

Section: Ilc2 In Skin Allergysupporting

confidence: 92%

“…ILC2 that were resident in the skin of healthy control subjects, and which increased in frequency and expressed elevated ST2, IL-17BR, TSLPR, and KLRG1 in skin biopsies from the lesions of patients with AD (45). Increased transcripts encoding IL-33 and IL-25 were also detected in the cells in acute lesional atopic dermatitis skin as compared with control subjects, and in vitro cultured human ILC2 released type-2 cytokines and amphiregulin in response to IL-33 stimulation.…”

Section: Ilc2 In Skin Allergymentioning

confidence: 97%

“…AD is associated with barrier dysfunction, and adaptive immune responses to common environmental allergens, characterized by the presence of Th2 cells and high levels of IL-13 and IL-4, have been detected in AD lesions (43,44). The recent discovery of ILC2 has led to the investigation of the potential involvement of these cells in this disease, and ILC2 cells have been reported to have an increased frequency in mouse and human atopic lesional skin (43,45). Both studies report the increased frequency of ILC2 in AD skin but offer different conclusions as to the critical cytokines responsible for ILC2 function in AD.…”

Section: Ilc2 In Skin Allergymentioning

confidence: 99%

“…Both studies report the increased frequency of ILC2 in AD skin but offer different conclusions as to the critical cytokines responsible for ILC2 function in AD. Kim and colleagues reported that TSLP acted independently of IL-33 in mouse and human skin (43), and Salimi and colleagues found that IL-25, IL-33, and TSLP could all activate mouse and human skin ILC2 (45).…”

Section: Ilc2 In Skin Allergymentioning

confidence: 99%

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Type-2 Innate Lymphoid Cells in Asthma and Allergy

McKenzie

2014

Annals ATS

115

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Type-2 innate lymphoid cells (ILC2) belong to an expanding family of innate lymphocytes that provide a potent source of immune effector cytokines at the initiation of immune responses. ILC2 arise, under the control of the transcription factors RORa and GATA3, from lymphoid progenitors in the bone marrow, to secrete type-2 cytokines including IL-5 and IL-13. Using experimental models, ILC2 have been implicated in allergic diseases, such as asthma and atopic dermatitis, but also in metabolic homeostasis. Furthermore, recent reports have indicated that ILC2 not only play roles at the initiation of type-2 immunity but can also contribute to chronic pathology, such as fibrosis, and can impact on the priming of the adaptive T-cell response. The identification of ILC2 in patients with allergic dermatitis and allergic rhinitis indicates that these cells may represent new therapeutic targets.Keywords: type-2 immunity; type-2 innate lymphoid cells; innate immunity; cytokines However, a recent major paradigm shift has added another layer of complexity to immunoregulation by cytokines with the discovery of innate lymphoid cells (ILCs) (2). ILCs produce many Th cell-associated cytokines but do not express cell surface markers associated with other immune cell lineages (lineage-negative [Lin 2 ]) and do not express a T-cell receptor. The ILC family now includes ILC1 (predominantly IFN-g-expressing cells), ILC2 (predominantly IL-5-and IL-13-expressing cells), and ILC3 (predominantly IL-22-and IL-17-expressing cells) (3-6). Due to their recent discovery, our knowledge of these cells is still rather rudimentary, but major roles are emerging for ILCs in protective immunity against parasitic helminths (ILC2) (7-9) and bacteria (ILC1 and ILC3) (10-12), and in autoimmune disorders (ILC1 and ILC3) (13), allergic disease (ILC2) (14-16), and obesity (17)(18)(19).Recent comprehensive reviews have described the identification and phenotypic characterization of 20). This review focuses on the most recent advances in our understanding of the factors that regulate ILC2 development and how these cells contribute to allergy and lung inflammation. ILC2ILC2 are found in the blood, spleen, intestine, liver, lung, fat-associated lymphoid clusters, and lymph nodes of mice (7-9). They are Lin 2 (CD3CD4CD8CD19CD11bCD11cFceR1 NK1.1Gr1 2 ) CD45 1 CD127

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Section: Ilc2 In Skin Allergysupporting

confidence: 92%

Section: Ilc2 In Skin Allergymentioning

confidence: 97%

Section: Ilc2 In Skin Allergymentioning

confidence: 99%

Section: Ilc2 In Skin Allergymentioning

confidence: 99%

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Type-2 Innate Lymphoid Cells in Asthma and Allergy

McKenzie

2014

Annals ATS

115

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“…In this regard, cutaneous allergic inflammation and dermatitis can be elicited by IL-2-induced proliferation of skin-resident ILC2 (Roediger et al 2013), or via IL-33/IL-25-and/or TSLPdriven ILC2 responses (Imai et al 2013;Kim et al 2012;Salimi et al 2013). Furthermore, human ILC2 express skin-homing receptors and are elevated in atopic lesions from human patients (Salimi et al 2013).…”

Section: Role Of Ilc2 In the Pathogenesis Of Allergic Inflammationmentioning

confidence: 99%

Innate Lymphoid Cells in Type 2 Immune Responses

Mirchandani

Salmond

2014

Arch. Immunol. Ther. Exp.

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In recent years, several distinct innate lymphoid cell populations (ILC) have been characterized in mice and humans. Group 2 ILC function as a rapid responder population in type 2 immune responses. Thus, a wealth of data has implicated an important role for ILC2 in immunity to parasitic infection and in immune pathology in inflammatory and allergic responses. In this review, we describe recent progress in our understanding of the development and ontogeny of ILC2 populations and the mechanisms by which these cells function in a variety of infection and disease settings. Finally, we emphasize recent findings indicating functional interactions between these innate cells and their adaptive CD4 ? Th2 cell counterparts.

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Innate Lymphoid Cells

Cousins

Weston

2015

Encyclopedia of Life Sciences

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Innate lymphoid cells (ILCs) are white blood cells derived from a common progenitor in the bone marrow. They respond rapidly to a limited array of antigens at the site of infection to provide immediate protection. The first identified ILCs were natural killer cells. However, several non‐cytotoxic members of the family have since been reported. All ILCs lack the rearranged antigen receptors characteristic of T‐ and B‐cells but can be similarly divided into three main groups based on cell surface markers and cytokine expression profiles. Similar to their adaptive immune response counterparts, they play specific roles in providing host defence against different pathogens. In addition, there is growing evidence that ILCs can contribute to multiple inflammatory and autoimmune diseases. Key Concepts ILCs are lymphocytes of the innate immune system and provide a rapid response to invading pathogens. ILCs lack the specific antigen receptors found on cells of the adaptive immune system. Development of ILCs is governed by sequential expression of different transcription factors and proceeds from a common precursor found in the bone marrow. Differential expression of cell surface markers and cytokines allows ILCs to be grouped into three families, each having a different role in host immunity. ILCs respond to signals released from epithelial and other cells to provide a rapid source of cytokines that can recruit other immune cells and stimulate tissue repair. The dysregulation of ILC activation has been linked to several human inflammatory and autoimmune diseases.

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A role for IL-25 and IL-33–driven type-2 innate lymphoid cells in atopic dermatitis

Abstract: 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

Cited by 841 publications

References 45 publications

Type-2 Innate Lymphoid Cells in Asthma and Allergy

Type-2 Innate Lymphoid Cells in Asthma and Allergy

Innate Lymphoid Cells in Type 2 Immune Responses

Innate Lymphoid Cells

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