Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells

Roediger, Ben; Kyle, Ryan; Yip, Kwok Ho; Sumaria, Nital; Guy, Thomas V.; Kim, Brian; Mitchell, Andrew J.; Tay, Szun S.; Jain, Rohit; Forbes-Blom, Elizabeth; Chen, Xi; Tong, Philip L.; Bolton, Holly A.; Artis, David; Paul, William E.; Groth, Barbara Fazekas de St; Grimbaldeston, Michele A.; Gros, Graham Le; Weninger, Wolfgang

doi:10.1038/ni.2584

Cited by 416 publications

(577 citation statements)

References 50 publications

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“…Thus, IL-2 induces ILC2 proliferation and enhances their production of IL-5 and IL-13. Furthermore, while this manuscript was under revision, it was reported that injection of RAG 2/2 mice with IL-2-IL-2 mAb complexes stimulated ILC2 proliferation in vivo (25). Previously, a stimulatory function of IL-2 in the induction of ILC2 IL-9 production was reported (16).…”

Section: Discussionmentioning

confidence: 88%

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Mirchandani

Besnard

Yip

et al. 2014

The Journal of Immunology

273

276

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CD4+ T cells have long been grouped into distinct helper subsets on the basis of their cytokine-secretion profile. In recent years, several subsets of innate lymphoid cell have been described as key producers of these same Th-associated cytokines. However, the functional relationship between Th cells and innate lymphoid cells (ILCs) remains unclear. We show in this study that lineage-negative ST2+ICOS+CD45+ type 2 ILCs and CD4+ T cells can potently stimulate each other’s function via distinct mechanisms. CD4+ T cell provision of IL-2 stimulates type 2 cytokine production by type 2 ILCs. By contrast, type 2 ILCs modulate naive T cell activation in a cell contact–dependent manner, favoring Th2 while suppressing Th1 differentiation. Furthermore, a proportion of type 2 ILCs express MHC class II and can present peptide Ag in vitro. Importantly, cotransfer experiments show that type 2 ILCs also can boost CD4+ T cell responses to Ag in vivo.

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Section: Discussionmentioning

confidence: 88%

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Mirchandani

Besnard

Yip

et al. 2014

The Journal of Immunology

273

276

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“…Mast cell degranulation is caused predominantly by IgE/FceRI crosslinking, and these data suggest that ILC2 may be attracted and activated during the adaptive type-2 response. It is noteworthy that intravital imaging of mouse ILC2 in the skin indicated that they interacted with mast cells and produced IL-13 (53). Another eicosanoid signaling pathway has also been reported for mouse lung ILC2.…”

Section: Ilc2 In Skin Allergymentioning

confidence: 79%

Type-2 Innate Lymphoid Cells in Asthma and Allergy

McKenzie

2014

Annals ATS

112

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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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“…Imaging studies have shown that ILC2 appear to ''patrol'' the skin slowly as compared with resident T cells (Roediger et al 2013). Furthermore, ILC2 interact with other skin-resident cells, including dermal mast cells.…”

Section: Ilc2 Responses In Infectionmentioning

confidence: 99%

“…Furthermore, ILC2 interact with other skin-resident cells, including dermal mast cells. The functional significance of these interactions has yet to be fully elucidated, nonetheless these studies are suggestive of a role for dermal ILC2 in immunosurveillance within this organ (Roediger et al 2013). …”

Section: Ilc2 Responses In Infectionmentioning

confidence: 99%

“…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%

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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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Cutaneous immunosurveillance and regulation of inflammation by group 2 innate lymphoid cells

Cited by 416 publications

References 50 publications

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Type 2 Innate Lymphoid Cells Drive CD4+ Th2 Cell Responses

Type-2 Innate Lymphoid Cells in Asthma and Allergy

Innate Lymphoid Cells in Type 2 Immune Responses

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