Advances in Skin, Wound Care and Tissue Science

Biography

Biography: Edgar Serfling

Abstract

Psoriasis is a chronic inflammatory skin disease that affects 2-3% of population in Western countries. Since B cells are hardly detected in psoriatic skin, until recently their role in psoriasis remained un-regarded. We show here that the repetitive epicutaneous application of Aldara®, a cream containing the toll-like reptor (TLR) 7-agonist imiquimod (IMQ), to mice induces skin inflammation that exhibits many aspects of early stages of human psoriasis. Mice depleted of B cells or bearing IL-10-deficient B cells show an even more fulminant inflammation upon IMQ exposure indicating that IL-10 synthesized in B cells controls skin inflammation. In contrast, ablation of NFATc1 in B cells results in depressed IMQ-induced skin inflammation. Aldara® cream application to the skin leads to the differentiation of splenic B cells to plasmablasts and IL-10-producing B cells. In vitro, IMQ induces the proliferation and IL-10 expression of splenic B cells. The induction of IL-10 RNA by IMQ can be blocked by a-IgM-mediated B cell receptor signals that, on the other hand, induce NFATc1. By binding to HDAC1, NFATc1 suppresses IL-10 expression, which, otherwise, dampens the production of inflammatory cytokines by T cells, including TNFa and IL-17. These data indicate a close link between NFATc1 and IL-10 expression in B cells during IMQ-mediated skin inflammation and suggest that the suppression of NFATc1 activity might be of benefit to treat human psoriasis and, possibly, other autoimmune diseases as well.