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 CD25 ) cells were increased, but Tfr (CD4 CXCR5 CD127 CD25 ) 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 PD-1 ) Tfh cells and Tfr cells were dramatically increased, but central memory (CCR7 PD-1 ) 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.

Dysregulated TFR and TFH cells correlate with B‐cell differentiation and antibody production in autoimmune hepatitis

“…Although TFR cells are known to be important regulators of autoimmune responses in human, the precise role of TFR cell in the pathogenic processes of AIH remains unclear. This study showed sufficient evidence that dysregulated between TFR and TFH cells contribute to the immunopathological process in AIH.…”

“…Several studies have showed that abnormal TFR cells activity might cause the destruction of immune tolerance and thereby lead to the immunopathogenesis of autoimmune diseases . Additionally, like TFH cell, TFR cells are also present in the peripheral circulation, the levels of which are directly correlated with a variety of human immunological disorders, such as primary biliary cholangitis (PBC) and multiple sclerosis(MS) . However, to the best of our knowledge, there are no reports of circulating TFR cells in patients with newly diagnosed AIH.…”

Follicular regulatory T cells: a novel target for immunotherapy?

“…Systemic AIDs involve rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), ankylosing spondylitis (AS), IgG4‐related disease (IgG4‐RD) and common variable immune deficiency (CVID) . Organ‐specific AIDs involve multiple sclerosis (MS), myasthenia gravis (MG), Hashimoto's thyroiditis (HT), primary biliary cholangitis (PBC), type 1 diabetes (T1D) and ulcerative colitis (UC) . It is also demonstrated that when the regulatory capacity of Tfr cells is impaired, the expansion of Tfr cells is accompanied by the development of autoimmunity in mice …”

“…Decreased cTfr cells and increased cTfh cells are found in patients with PBC . Meanwhile, both ICOS + cTfr cells and CTLA‐4 + cTfh cells are increased, and the ratio of cTfr/cTfh is inversely correlated with disease progression, drug response and the level of serum IgM.…”

“…76 Decreased cTfr cells and increased cTfh cells are found in patients with PBC. 77 Meanwhile, both ICOS + cTfr cells and CTLA-4 + cTfh cells are increased, and the ratio of cTfr/cTfh is inversely correlated with disease progression, drug response and the level of serum IgM. The effector memory phenotype (CCR7 lo PD-1 hi ) in cTfr cells and cTfh cells is significantly increased, while the central memory phenotype (CCR7 hi PD-1 lo ) is decreased in PBC patients, and the frequency of effector memory cTfr cells is positively correlated with the level of serum alkaline phosphatase.…”