Intestinal inflammation alters the antigen-specific immune response to a skin commensal

Cell Rep. 2022 May 31;39(9):110891. doi: 10.1016/j.celrep.2022.110891.

Abstract

Resident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic skin disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal skin colonization by Staphylococcus epidermidis facilitates generation of commensal-specific tolerance and CD4+ regulatory T cells (Tregs), we ask whether this response is perturbed by gut inflammation. Chemically induced colitis is accompanied by intestinal expansion of S. epidermidis and reduces gut-draining lymph node (dLN) commensal-specific Tregs. It also results in reduced commensal-specific Tregs in skin and skin-dLNs and increased skin neutrophils. Increased CD4+ circulation between gut and skin dLN suggests that the altered cutaneous response is initiated in the colon, and resistance to colitis-induced effects in Cd4creIl1r1fl/fl mice implicate interleukin (IL)-1 in mediating the altered commensal-specific response. These findings provide mechanistic insight into observed connections between inflammatory skin and intestinal diseases.

Keywords: CP: Immunology; CP: Microbiology; S. epidermidis; colitis; commensal; commensal-specific T cells; gut-skin axis; inflammation; intestinal immunity; regulatory T cells; skin immunity; skin microbiome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Colitis* / chemically induced
  • Immunity*
  • Inflammation
  • Mice
  • Skin
  • Staphylococcus epidermidis
  • T-Lymphocytes, Regulatory