Neonatal Tregs Suppress the Development of a Stromal Niche for Th2 Cells in Skin

• DOI: 10.4049/jimmunol.204.supp.157.1
• Publication Date: 2023-01-01T13:55:48Z
• Authors: Ian C Boothby; Ireneusz Habrylo; Devi P Boda; Michael D Rosenblum
• Keywords: Immune Dysregulation

Abstract Many allergic diseases originate during early life and cause chronic inflammation that persists into adulthood. Immune dysregulation the “critical window” of postnatal development has been hypothesized to establish lifelong susceptibility inflammation; however, mechanistic evidence is lacking. Regulatory T cells (Tregs) are critical suppressors autoimmunity functionally unique life. We have found neonatal Tregs (neoTregs) suppress profound dysfunction skin immunity stromal architecture in neonates but not adults. Transient depletion neoTregs results aberrant outgrowth fibrous bands subcutis. Single cell RNA sequencing subsequent validation studies revealed these composed a novel “type 2” fibroblast celltype localizes subcutis expresses alarmins IL-18 IL-33. Concurrently, Th2 accumulate neoTreg-depleted persist through These reside near type 2 fibroblasts subcutis, genetic ablation or IL-33 reduces their accumulation. Collectively, data suggest formation sustained niche supports pathogenic skin-resident may predispose disease later findings advance our understanding how immune arrive peripheral tissues be relevant human disease.