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

bioRxiv : the preprint server for biology | 2023

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.

Pubmed ID: 37873143 RIS Download

Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK063720
  • Agency: NIAMS NIH HHS, United States
    Id: R01 AR080034
  • Agency: NIAID NIH HHS, United States
    Id: DP2 AI144968
  • Agency: NIH HHS, United States
    Id: S10 OD021822
  • Agency: NIAMS NIH HHS, United States
    Id: K99 AR079554

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