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Homeostatic IL-13 in healthy skin directs dendritic cell differentiation to promote T H 2 and inhibit T H 17 cell polarization
Ist Teil von
Nature immunology, 2021-12, Vol.22 (12), p.1538
Ort / Verlag
United States
Erscheinungsjahr
2021
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
The signals driving the adaptation of type 2 dendritic cells (DC2s) to diverse peripheral environments remain mostly undefined. We show that differentiation of CD11b
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
and showed defective activation in response to allergens, with diminished ability to support the development of IL-4
GATA3
helper T cells (T
), whereas antifungal IL-17
RORγt
T
cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.