Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation.

Autor:	Dhariwala MO; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., DeRogatis AM; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Okoro JN; Department of Dermatology, University of California San Francisco; San Francisco, CA USA.; Biomedical Sciences Program, University of California San Francisco; San Francisco, CA USA., Weckel A; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Tran VM; Department of Dermatology, University of California San Francisco; San Francisco, CA USA.; Biomedical Sciences Program, University of California San Francisco; San Francisco, CA USA., Habrylo I; Department of Dermatology, University of California San Francisco; San Francisco, CA USA.; Biomedical Sciences Program, University of California San Francisco; San Francisco, CA USA., Ojewumi OT; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Tammen AE; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Leech JM; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Merana GR; Department of Dermatology, University of California San Francisco; San Francisco, CA USA.; Biomedical Sciences Program, University of California San Francisco; San Francisco, CA USA., Carale RO; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Barrere-Cain R; Department of Dermatology, University of California San Francisco; San Francisco, CA USA., Hiam-Galvez KJ; Biomedical Sciences Program, University of California San Francisco; San Francisco, CA USA.; Department of Otolaryngology-Head and Neck Surgery, Department of Microbiology and Immunology, Parker Institute for Cancer Immunotherapy, University of California San Francisco; San Francisco, CA USA., Spitzer MH; Department of Otolaryngology-Head and Neck Surgery, Department of Microbiology and Immunology, Parker Institute for Cancer Immunotherapy, University of California San Francisco; San Francisco, CA USA., Scharschmidt TC; Department of Dermatology, University of California San Francisco; San Francisco, CA USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2023 Oct 02. Date of Electronic Publication: 2023 Oct 02.
DOI:	10.1101/2023.09.29.560039
Abstrakt:	Early life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory towards health versus disease. Monocytes, macrophages and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin. Transient postnatal depletion of these monocytes resulted in heightened IL-17A production by skin T cells, which was particularly sustained among CD4 + T cells into adulthood and sufficient to exacerbate inflammatory skin pathologies. Neonatal skin monocytes were enriched in expression of negative regulators of the IL-1 pathway. Functional in vivo experiments confirmed a key role for excessive IL-1R1 signaling in T cells as contributing to the dysregulated type 17 response in neonatal monocyte-depleted mice. Thus, a commensal-driven wave of monocytes into neonatal skin critically facilitates long-term immune homeostasis in this prominent barrier tissue. Competing Interests: T.C.S is on the scientific advisory board of Concerto Biosciences. M.H.S. is founder, shareholder and board member of Teiko.bio, has received a speaking honorarium from Fluidigm Inc., Kumquat Bio, and Arsenal Bio, has been a paid consultant for Five Prime, Ono, January, Earli, Astellas, and Indaptus, and has received research funding from Roche/Genentech, Pfizer, Valitor, and Bristol Myers Squibb.
Databáze:	MEDLINE
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