Integrin alpha 4 beta 1-dependent regulatory B-cell migration into the skin limits cutaneous inflammation

Abstract B cells continuously recirculate through the skin. However, their localized functions within the cutaneous environment are still largely unknown. A subset of IL-10+ B regulatory cells (Bregs) migrate into inflamed skin in an α4β1-integrin-dependent manner, thus we hypothesize that an impaired skin-migration of these Bregs could aggravate skin inflammation. Using two types of skin inflammation (IMQ-induced psoriasiform and DNFB-mediated delayed contact hypersensitivity) in a mouse model with a B cell-specific inducible deletion of α4β1-integrin, we found that loss of α4β1-integrin expression in B cells led to a significant decrease in the numbers of IL-10+ B cells in the inflamed skin without affecting their numbers in lymphoid tissues. The reduced homing of Bregs into the inflamed skin was associated with a significant increase in the clinical and histopathological parameters of cutaneous inflammation in both mouse models. Additionally, transfer of IL-10 competent B cells into Bregs-deficient mice lead to a significant improvement in the psoriasiform skin phenotype. Thus, our data show a key role for skin-homing IL-10+ Bregs in the suppression of skin inflammation, supporting the notion that Bregs are critical players in the cutaneous environment during inflammatory skin diseases.