157 IL-10+ regulatory B cell migration into inflamed skin limits cutaneous inflammation

Abstract

To maintain skin homeostasis several types of leukocytes exist in or are recruited into the skin. While most of these leukocytes are well characterized, the roles of skin-associated B cells remain largely unknown. Our lab previously demonstrated that a subset of IL-10+ regulatory B cells preferentially migrates into the inflamed skin of mice, a process that required α4β1 integrin. Thus, we hypothesized that B regulatory cells suppress skin inflammation and that impaired migration of these cells into the skin exacerbates skin inflammation. To test this hypothesis, we used two mouse models of skin inflammation: (i) IL-17-dominated psoriasiform skin inflammation induced by imiquimod (IMQ) cream and (ii) IFN-γ-mediated cutaneous delayed contact hypersensitivity elicited by dinitrofluorobenzene (DNFB). Furthermore, we employed a mouse model with a B cell-specific tamoxifen-inducible deletion of α4-integrin (Itga4). Here, we found that inducing the deletion of Itga4 in B cells led to a significant decreased in skin-associated IL-10+ B cells in inflamed skin and included both conventional B2 (CD19+B220highCD43-) and innate-like B1 (CD19+B220-/lowCD43+) cells. The decrease accumulation of IL-10+ regulatory B cells was associated with a significant increase in the clinical and histopathological parameters of skin inflammation in both skin inflammation models. Thus, our data show a crucial function of skin-homing IL-10+ regulatory B cells in the suppression of IL-17- and IFN-γ-dominated skin inflammation; supporting the notion that B regulatory cells are critical players in the cutaneous environment during inflammatory skin diseases.