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

Abstract

ObjectiveSystemic 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.MethodsThirty 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.ResultsFrequencies of CD4+CXCR5+CD45RA-effector cTfh cells, PD1+cTfh, PD1+ICOS+cTfh, PD1+cTfh1, PD1+cTfh2, PD1+cTfh17, and PD1+ICOS+cTfh1 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 PD1+ICOS+ cTfh or PD1+ICOS+ cTfh1 cell frequencies and plasmablasts or IL-21 levels, as well as between plasmablasts. We also found PD1+ICOS+ 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.ConclusionTfh cell subsets and plasmablasts may play a fundamental role in the pathogenesis of SLE and may provide potential targets for therapeutic interventions for SLE.

Imbalance of follicular regulatory T (Tfr) cells/follicular helper T (Tfh) cells in adult patients with primary immune thrombocytopenia

“…Similar to the findings in SLE 26 and UC 27 patients, this study showed Tfr/Tfh imbalance in untreated ITP patients. This is also consistent with the results by Chen et al 28 This imbalance manifests as an increase in Tfh cells and may further promote the Tfh-mediated B-cell response, 29,30 leading to the production of excessive antibodies, mediating the destruction of PLT, and possibly inducing or promoting the occurrence of ITP.…”

Identification of Biomarkers in Affected Hair Follicles from Chronic Discoid LupusErythematosus by Weighted Gene Co-Expression Network Analysis

“…Relevant result has not seen in CDLE skin samples 33 . Similar expansion was observed in peripheral blood samples from SLE patients, and that can be inhibited to ameliorate SLE 34,35 . Interestingly, the B cells, including B cells and plasma cells, underwent a step wise decrease in N, C, D groups in contrast to that a greater Bcell in ltrate was found in CDLE skin lesions 36,37 .…”

Clinical and immunological features of COVID‐19 in patients with anti‐MDA5 dermatomyositis during the omicron wave in Chongqing, China

“…This subset acts as effector cells that induce B-cell differentiation, and antibody secretion, and regulate immunoglobulin isotype switching. 41 Concerning the cellular response, our data showed a significant reduction in WTspecific CD4 + T cells and CD8 + T cells in patients with anti-MDA5 DM compared to HCs after COVID-19 infection. This suggested that the cellular immune responses may be impaired in patients with anti-MDA5 DM after COVID-19 infection.…”