Follicular regulatory T cell biology and its role in immune-mediated diseases

Follicular regulatory T (Tfr) cells are recently found to be a special subgroup of regulatory T (Treg) cells. Tfr cells play an important role in regulating the germinal center (GC) response, especially modulating follicular helper T (Tfh) cells and GC-B cells, thereby affecting the production of antibodies. Tfr cells are involved in the generation and development of many immune-related and inflammatory diseases. This article summarizes the advances in several aspects of Tfr cell biology, with special focus on definition and phenotype, development and differentiation, regulatory factors, functions, and interactions with T/B cells and molecules involved in performance and regulation of Tfr function. Finally, we highlight the current understanding of Tfr cells involvement in autoimmunity and alloreactivity, and describe some drugs targeting Tfr cells. These latest studies have answered some basic questions in Tfr cell biology and explored the roles of Tfr cells in immune-mediated diseases.