TSLP elicits IL-33-independent innate lymphoid cell responses to promote skin inflammation.
Innate 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.
Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Brian S
BS
Kim
Mark C
MC
Siracusa
Steven A
SA
Saenz
Mario
M
Noti
Laurel A
LA
Monticelli
Gregory F
GF
Sonnenberg
Matthew R
MR
Hepworth
Abby S
AS
Van Voorhees
Michael R
MR
Comeau
David
D
Artis
D056704:Adaptive Immunity; D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D003876:Dermatitis, Atopic / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D000067596:Interleukin-33; D007378:Interleukins / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D012867:Skin / Q000276:immunology / Q000473:pathology*; D000094632:Thymic Stromal Lymphopoietin
D016207:Cytokines; C506536:IL33 protein, human; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D007378:Interleukins; D000094632:Thymic Stromal Lymphopoietin