Commensal myeloid crosstalk in neonatal skin regulates long-term cutaneous type 17 inflammation
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 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. Overall design: We performed scRNA sequencing on immune cells in the skin of D15 mice that were either depleted of monocytes by treating with the anti-Gr-1 antibody (aGr1) or with an isotype control. CD45+ cells were FACS sorted from the skin of mice in each condition. Cells from 4-7 mice were pooled for each ocndition.