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Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote TH2 and inhibit TH17 cell polarization


The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11b(lo) 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 CD11b(hi) 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(+)RORgammat(+) TH cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.

Type Journal
ISBN 1529-2916 (Electronic) 1529-2908 (Linking)
Authors Mayer, J. U.; Hilligan, K. L.; Chandler, J. S.; Eccles, D. A.; Old, S. I.; Domingues, R. G.; Yang, J.; Webb, G. R.; Munoz-Erazo, L.; Hyde, E. J.; Wakelin, K. A.; Tang, S. C.; Chappell, S. C.; von Daake, S.; Brombacher, F.; Mackay, C. R.; Sher, A.; Tussiwand, R.; Connor, L. M.; Gallego-Ortega, D.; Jankovic, D.; Le Gros, G.; Hepworth, M. R.; Lamiable, O.; Ronchese, F.
Responsible Garvan Author Dr David Gallego-Ortega
Published Date 2021-12-31
Published Volume 22
Published Issue 12
Published Pages 1538-1550
Status Published in-print
DOI 10.1038/s41590-021-01067-0
URL link to publisher's version