T-cell plasticity in inflammatory skin diseases--the good, the bad, and the chameleons.

Abstract

According to the concept of T-cell plasticity, peripheral T cells - once differentiated into a specific T cell subset - may, in response to new environmental cues or signaling alterations, adopt the phenotype of a different helper cell subset with regard to cytokine production and regulatory functions. In a variety of T cell-mediated inflammatory disorders, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis, T-cell plasticity - in particular the conversion of regulatory T cells (Tregs) to IL-17-producing inflammatory cells - has recently been described as key pathomechanism contributing to the aggravation of inflammatory symptoms and disease chronification. Apart from psoriasis, the phenomenon of immune cell plasticity may also have a role in other inflammatory conditions of the skin showing a T cell component and/or an IL-17-mediated pathology, such as lichen planus, lupus erythematosus, blistering diseases, allergic disorders, and others. This review summarizes the basic molecular mechanisms regulating T-cell fate decisions and plasticity in inflamed skin and in other lymphoid organs. Moreover, it explores the effect of established targeted therapies as well as alternative concepts with a focus on how to prevent the unwanted conversion of "helpful" T cells and other beneficial immune cells to pathological inflammatory vermin.