Mouse skin CD45 cells in house dust mite dermatitis
Despite robust literature associating IL-31 with pruritic inflammatory skin diseases, its influence on cutaneous inflammation and on the interplay between inflammatory and neurosensory pathways remain unmapped. Here, we examined the consequences of disrupting Il31 and its receptor Il31ra in a mouse model of house dust mite (HDM) allergic dermatitis. Il31-deficient mice displayed an increased number and proportion of cutaneous type 2 cytokine-producing CD4 T cells and serum IgE in response to HDM. Single cell RNA-sequencing analysis of skin CD45+ populations from HDM-treated skin revealed that Il4ra+ monocytes and macrophages capable of fueling a feedforward type 2 inflammatory loop were selectively enriched in Il31ra-deficient HDM dermatitis skin. Thus, IL-31 is not strictly a pro-inflammatory cytokine, but rather an immunoregulatory factor that limits the magnitude of type 2 inflammatory responses in skin. Overall design: To determine the contribution of IL-31 to skin inflammation in dust mite-induced dermatitis, we epicutaneously challenged WT C57Bl/6 (B6_HDMw3) and IL31RAKO (B6_IL31RAKO_HDMw3) with Biostir HDM ointment. HDM-treated skin pooled from 4 mice per group (B6_WT or B6_IL31RAKO) was harvested and digested with liberase, hyaluronidase, and DNAse. Viable CD45+ skin cells from each experimental group (WT_HDM and IL31RAKO_HDM) were isolated by FACS-sorting in preparation for RNA sequencing.