Skin-Homing Regulatory B Cells Required for Suppression of Cutaneous Inflammation

Abstract

Pro and anti-inflammatory B-cell subsets that localize to unperturbed and inflamed skin are newly emerging components of the skin immune system. To test the relevance of regulatory B cells (Bregs) in the suppression of cutaneous inflammation, we asked whether impaired migration of these cells into the skin exacerbates skin inflammation. Using a mouse model with a B-cell‒specific tamoxifen-inducible deletion of α4β1 integrin, we demonstrate that selective disruption of α4β1-integrin expression in B cells significantly decreases IL-10⁺ Bregs in inflamed skin, whereas it does not affect their counterparts in lymphoid tissues. Impaired skin homing and reduced cutaneous accumulation of IL-10⁺ Bregs lead to a significant increase in clinical and histopathological parameters of inflammation in both psoriasiform skin inflammation and cutaneous delayed contact hypersensitivity. Thus, our data show a crucial function of 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.