Deficiency in T follicular regulatory cells promotes autoimmunity

Abstract

Fu et al. analyze Bcl6fl/flFoxp3Cre/Cre mice and show that Tfr deficiency enhances immunity to influenza virus but promotes autoimmunity, which sheds new light on the understanding and treatment of autoimmune diseases.

T follicular regulatory (Tfr) cells: Dissecting the complexity of Tfr‐cell compartments

“…35,[40][41][42][43] Given that several redundant mechanisms were pointed to induce tolerance within GC, it is notable that the absence of Tfr cells alone can be sufficient to induce autoantibody-mediated autoimmunity. 35,[40][41][42][43] Given that several redundant mechanisms were pointed to induce tolerance within GC, it is notable that the absence of Tfr cells alone can be sufficient to induce autoantibody-mediated autoimmunity.…”

“…[144][145][146] Blood Tfr cells were also found increased in HBV and HCV chronically infected patients, as well as in patients with helminth infections. 15,35,43 Indeed, the use of different strategies for Tfr-cell identification in human autoimmune diseases provided inconsistent results. 15,35,43 Indeed, the use of different strategies for Tfr-cell identification in human autoimmune diseases provided inconsistent results.…”

Follicular regulatory T cells: a novel target for immunotherapy?

“…67 Impaired cTfr cells contribute to decreased saliva flow rates and enhanced salivary gland-specific antibodies, tissue destruction and IgG deposition in a mouse experimental SS model, indicative of the development of disease. 81 Percentages of cTfr cells and cTfh cells are significantly higher in patients with AS. 68 In addition, the frequency of cTfr cells is negatively associated with serum IgA in AS patients before treatment and is negatively associated with cTfh cells and the level of serum IL-21 after 1 month of standard treatment in drug responders.…”

“…Thus, the increased frequency of the cTfr cells indicates ongoing humoral activity, and the cTfr/cTfh ratio is suggested to be considered as a strong predictor of SS diagnosis and focal sialadenitis in patients suffering sicca symptoms . Impaired cTfr cells contribute to decreased saliva flow rates and enhanced salivary gland–specific antibodies, tissue destruction and IgG deposition in a mouse experimental SS model, indicative of the development of disease …”

“…Botta et al found that Tfr cells in the lung‐draining mediastinal LNs fail to accumulate at the peak of influenza infection, but after the immune response subsides, a fraction of Treg cells downregulates CD25 and then differentiates into Tfr cells. Tfr cell–deficient mice exhibit enhanced immunity to influenza viruses, indicating that Tfr cells may be targets in infectious disease . Using mice infected with orthopox and influenza A viruses, it was observed that Tfh cells expand more prominently than Tfr cells and that both lymphoid and circulating Tfh/Tfr ratios can be regarded as early predictors of long‐lived protective humoral immune responses …”