期刊
NATURE IMMUNOLOGY
卷 22, 期 12, 页码 1538-+出版社
NATURE PORTFOLIO
DOI: 10.1038/s41590-021-01067-0
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资金
- Independent Research Organization grant from the Health Research Council of New Zealand (HRC) [18-1003, 18-510]
- Marjorie Barclay Trust
- Malaghan Institute Postdoctoral Fellowship
- Intramural Research Program of the NIAID, NIH
- Sir Henry Dale Fellowship - Wellcome Trust [105644/Z/14/Z]
- Sir Henry Dale Fellowship - Royal Society [105644/Z/14/Z]
- Lister Institute of Preventative Medicine Prize
- EMBO long-term fellowship [ALTF 1209-2019]
- Wellcome Trust [105644/Z/14/Z] Funding Source: Wellcome Trust
The study demonstrates that IL-13 secreted by dermal innate lymphoid cells plays a crucial role in promoting the differentiation of a CD11b(lo) type 2 dendritic cell subset in the skin of mice and humans, supporting the development of T(H)2 cells and inhibiting T(H)17 cells. This homeostatic IL-13 fosters a noninflammatory skin environment conducive to allergic sensitization.
Ronchese and colleagues show that IL-13 secreted homeostatically by dermal ILCs contributes to the differentiation of a CD11b(lo) type 2 dendritic cell subset, which supports the development of T(H)2 cells and curtails the development of T(H)17 cells in the skin of mice and humans. 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 (T-H), whereas antifungal IL-17(+)ROR gamma t(+) T-H cells were increased. Therefore, homeostatic IL-13 fosters a noninflammatory skin environment that supports allergic sensitization.
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