- Merana, Geil R;
- Dwyer, Laura R;
- Dhariwala, Miqdad O;
- Weckel, Antonin;
- Gonzalez, Jeanmarie R;
- Okoro, Joy N;
- Cohen, Jarish N;
- Tamaki, Courtney M;
- Han, Jungmin;
- Tasoff, Preston;
- Palacios-Calderon, Yasmin;
- Ha, Connie WY;
- Lynch, Susan V;
- Segre, Julia A;
- Kong, Heidi H;
- Kattah, Michael G;
- Ma, Averil;
- Scharschmidt, Tiffany C
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.