Controllers of cutaneous regulatory T cells: ultraviolet radiation and the skin microbiome

Abstract For the maintenance of homeostasis termination of immune reactions is as equally important as their induction. In this scenario regulatory T cells (Treg) play an important role. Accordingly a variety of inflammatory diseases are caused by an impairment of Treg. Hence, it is important to identify triggers by which Treg can be induced and activated, respectively. For quite a long time it is known that ultraviolet radiation can induce Treg which inhibit cutaneous immune reactions including contact hypersensitivity. Since these Treg inhibit in an antigen-specific fashion they may harbor therapeutic potential. However similar Treg can be induced also by other triggers which include vitamin D and antimicrobial peptides. Recently it was discovered that the gut microbiome controls the development of Treg in the intestine. The same may apply for the skin. Short chain fatty acids, microbiota-derived bacterial fermentation products, appear to induce and to activate Treg in the skin. Topical application of short chain fatty acids was shown to inhibit contact hypersensitivity and to reduce inflammation in the murine imiquimod-induced psoriasis-like skin inflammation model. Together, these data indicate that induction and activation of Treg may be a potential therapeutic strategy to treat inflammatory diseases in the future.