Nature immunology · 2021
Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization.
СтатьяResearch Support, N.I.H., IntramuralПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Mayer Johannes U, Hilligan Kerry L, Chandler Jodie S, Eccles David A, Old Samuel I, Domingues Rita G, Yang Jianping, Webb Greta R, Munoz-Erazo Luis, Hyde Evelyn J, Wakelin Kirsty A, Tang Shiau-Choot, Chappell Sally C, von Daake Sventja, Brombacher Frank, Mackay Charles R, Sher Alan, Tussiwand Roxane, Connor Lisa M, Gallego-Ortega David, Jankovic Dragana, Le Gros Graham, Hepworth Matthew R, Lamiable Olivier, Ronchese Franca
Аннотация
The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11blo migratory DC2s-a DC2 population unique to the dermis-required IL-13 signaling dependent on the transcription factors STAT6 and KLF4, whereas DC2s in lung and small intestine were STAT6-independent. Similarly, human DC2s in skin expressed an IL-4 and IL-13 gene signature that was not found in blood, spleen and lung DCs. In mice, IL-13 was secreted homeostatically by dermal innate lymphoid cells and was independent of microbiota, TSLP or IL-33. In the absence of IL-13 signaling, dermal DC2s were stable in number but remained CD11bhi and showed defective activation in response to allergens, with diminished ability to support the development of IL-4+GATA3+ helper T cells (TH), whereas antifungal IL-17+RORγt+ TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.