Aberrant expansion of follicular helper T cell subsets in patients with systemic lupus erythematosus.

OBJECTIVE

Systemic lupus erythematosus (SLE) is a chronic and complex autoimmune disease characterized by multiple autoantibodies, resulting in multiple organ and tissue damages. These pathogenic autoantibodies produced by B cells are closely correlated with follicular helper T (Tfh) cell subsets that play a fundamental role in the pathogenesis of SLE. The aim of the present study was to study the phenotype and role of circulating Tfh (cTfh) cell subsets and associated B cell subpopulations in active and inactive SLE patients.

METHODS

Thirty SLE outpatients and 24 healthy controls (HCs) were enrolled in this study. The frequency of cTfh cell and B cell subsets in peripheral blood mononuclear cells (PBMCs) and the plasma levels of eight cytokines were determined by flow cytometry, and plasma IL-21 levels were measured by ELISA. Meanwhile, we used MRL/lpr mice as the model of SLE to research the alterations of Tfh cells in the thymus and spleen of mice.

RESULTS

Frequencies of CD4CXCR5CD45RAeffector cTfh cells, PD1cTfh, PD1ICOScTfh, PD1cTfh1, PD1cTfh2, PD1cTfh17, and PD1ICOScTfh1 cells as well as plasmablasts showed significant differences among HC, active and inactive SLE patients. Moreover, cytokines typically associated with cTfh cells, including IL-6 and IL-21, were elevated in active SLE patients compared to inactive SLE patients and HCs. Additionally, a positive correlation was observed between PD1ICOS cTfh or PD1ICOS cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1ICOS Tfh cells expansion in both thymus and spleen of MRL/lpr mice, accompanied by increased frequencies in B cells and plasmablasts, meanwhile, cTfh1which expressing IFN-γ was increased in the peripheral blood of MRL/lpr mice.

CONCLUSION

Tfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.