biostudies-literatureBoothby ICNIDDK NIH HHSNIAID NIH HHSNIAMS NIH HHSNIH HHSNIGMS NIH HHS667-672https://www.ebi.ac.uk/biostudies/studies/S-EPMC8906225biostudies-literatureUnknown599(7886)Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility¹. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (T_H2) cells within a distinct microanatomical niche. T_H2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as T_H2-interacting fNatureEarly-life inflammation primes a T helper 2 cell-fibroblast niche in skin.PMC8906225T32 GM007618P30 DK063720R01 AR077553R01 AR071944S10 OD021822T32 AR079068T32 AI007334R21 AI071944S10 OD021664F30 AI147364Cohen JNHabrylo IBoothby ICChan JDClancy SMcCalmont THBoda DPHarris HWLowe MMYates AENeuhaus IMPauli MKwan EYMolofsky ABRosenblum MDKinet MJfalseEarly-life inflammation primes a T helper 2 cell-fibroblast niche in skin.Inflammation early in life can prime the local immune milieu of peripheral tissues, which can cause lasting changes in immunological tone that confer disease protection or susceptibility¹. The cellular and molecular mechanisms that prompt changes in immune tone in many nonlymphoid tissues remain largely unknown. Here we find that time-limited neonatal inflammation induced by a transient reduction in neonatal regulatory T cells causes a dysregulation of subcutaneous tissue in mouse skin. This is accompanied by the selective accumulation of type 2 helper T (T_H2) cells within a distinct microanatomical niche. T_H2 cells are maintained into adulthood through interactions with a fibroblast population in skin fascia that we refer to as T_H2-interacting f2021-01-01T00:00:00Z2021 Nov2026-04-08T17:30:15.648Z2025-06-01T12:09:33.013ZS-EPMC89062253470729210.1038/s41586-021-04044-7