Dysregulation of Circulating Tfr/Tfh Ratio in Primary biliary cholangitis

Abstract

Follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells are critical for the development and maintenance of germinal centre (GC) and humoral immune responses. Accumulating evidence has demonstrated that the dysregulation of either Tfh cells or Tfr cells contributes to the pathogenesis of autoimmune diseases. We aim to investigate the roles of circulating Tfh cells and circulating Tfr cells in the pathogenesis of primary biliary cholangitis (PBC). A total of 34 patients with PBC and 27 health individuals were enrolled in this study. Flow cytometry revealed that circulating Tfh (CD4⁺ CXCR5⁺ CD127^hi CD25^lo ) cells were increased, but Tfr (CD4⁺ CXCR5⁺ CD127^lo CD25^hi ) cells and ratio of Tfr/Tfh were dramatically decreased in PBC patients compared with healthy controls. The Tfr/Tfh ratio was negatively correlated with level of serum IgM. Meanwhile, we also observed effector memory (CCR7^lo PD-1^hi ) Tfh cells and Tfr cells were dramatically increased, but central memory (CCR7^hi PD-1^lo ) Tfh cells and Tfr cells were decreased in PBC patients compared with healthy controls. Effector memory Tfr cells were positively correlated with level of serum ALP. These results indicate that an imbalance of circulating Tfr cells and Tfh cells may be involved in the immunopathogenesis of PBC and may provide novel insight for the development of PBC therapies.