TSLP Elicits IL-33-Independent Innate Lymphoid Cell Responses to Promote Skin Inflammation

Kim, B. S.; Siracusa, M. C.; Saenz, S. A.; Noti, Mario; Monticelli, L. A.; Sonnenberg, G. F.; Hepworth, M. R.; Van Voorhees, A. S.; Comeau, M. R.; Artis, D. (2013). TSLP Elicits IL-33-Independent Innate Lymphoid Cell Responses to Promote Skin Inflammation. Science translational medicine, 5(170), 170ra16-170ra16. American Association for the Advancement of Science 10.1126/scitranslmed.3005374

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nnate lymphoid cells (ILCs) are a recently identified family of heterogeneous immune cells that can be divided into three groups based on their differential developmental requirements and expression of effector cytokines. Among these, group 2 ILCs produce the type 2 cytokines interleukin-5 (IL-5) and IL-13 and promote type 2 inflammation in the lung and intestine. However, whether group 2 ILCs reside in the skin and contribute to skin inflammation has not been characterized. We identify a population of skin-resident group 2 ILCs present in healthy human skin that are enriched in lesional human skin from atopic dermatitis (AD) patients. Group 2 ILCs were also found in normal murine skin and were critical for the development of inflammation in a murine model of AD-like disease. Remarkably, in contrast to group 2 ILC responses in the intestine and lung, which are critically regulated by IL-33 and IL-25, group 2 ILC responses in the skin and skin-draining lymph nodes were independent of these canonical cytokines but were critically dependent on thymic stromal lymphopoietin (TSLP). Collectively, these results demonstrate an essential role for IL-33- and IL-25-independent group 2 ILCs in promoting skin inflammation.

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