TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation (P3040)

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Abstract Innate lymphoid cells (ILCs) are a recently identified family of immune cells that regulate inflammation and tissue repair at barrier surfaces such as the intestine and lung. Previous studies have demonstrated that group 2 ILCs found in the intestine or lung respond to the predominantly epithelial cell-derived cytokines IL-33 and IL-25 and produce the type 2 cytokines IL-5 and IL-13. However, whether group 2 ILCs are found in the skin, whether they respond to epithelial cell-derived cytokines and whether they contribute to skin inflammation has not been characterized. Here, we identified a population of skin-resident group 2 ILCs present in healthy human skin and enriched in lesional human skin isolated from atopic dermatitis (AD) patients. Group 2 ILCs were also found in normal murine skin, accumulated in the skin and skin-draining lymph nodes in a murine model of AD-like inflammation and were critical for the elicitation of type 2 cytokine responses and AD-like inflammation. Remarkably, ILC responses and AD-like inflammation were independent of IL-33 and IL-25 but 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.