New insights into the immunopathogenesis of systemic lupus erythematosus: the role of T follicular helper cells.

Objective To review the development of T follicular helper (T-FH) cells and their role in systemic lupus erythematosus (SLE) pathogenesis, the effect of dendritic cells (DCs) on T-FH cells in SLE, as well as the potential use of TFH cells as a new therapeutic target in clinical practice. Data sources The data used in this review were retrieved mainly from the PubMed database (1989-2013). The terms used in the literature search were "T follicular helper cells," "systemic lupus erythematosus," and "dendritic cells." Study selection Relevant publications about the T-FH cells development, the interaction between the T-FH cells and the DCs, and the clinical applications of T-FH cells were identified, retrieved, and reviewed. Results T-FH cells, a novel distinct CD4+ T cell subset, are specialized in providing help to B cells in the formation of germinal centers (GCs) and long-term protective humoral immune responses. The development of T-FH cells from naive CD4+ T cell is a multistep process. As the pivot of immunoregulation, DCs are indispensable for T-FH cells generation. In addition to receptor-ligand interactions between T-FH cells and DCs, the cytokines secreted by DCs are also necessary for T-FH cell generation. T-FH cell dysregulation has been implicated in the development of SLE. More evidence from animal models of SLE and SLE patients suggests that T-FH cells are necessary for pathogenic autoantibody production. Therefore, therapeutically targeting T-FH cells can be a promising approach to treat antibody-mediated autoimmune diseases including SLE. Conclusion T-FH cells play a critical role in the pathogenesis of SLE, making them attractive therapeutic targets in clinical practice.