Functional inhibition of regulatory CD4+CD25+T cells in peripheral blood of patients with pemphigus vulgaris

Abstract

Summary Background Pemphigus vulgaris (PV) is a potentially life‐threatening autoimmune bullous disease affecting the skin and mucous membranes. Its pathogenic mechanism is still not fully understood. Regulatory T cells (Tregs) have been reported to play a significant role in regulating immune homeostasis in autoimmune disorders, such as PV. Aim To investigate the potential role of Tregs in the immunopathogenesis of PV. Methods We enrolled 15 patients with PV and 15 healthy controls (HCs). Peripheral blood samples were collected from all participants before treatment. This was followed by flow cytometric, real‐time reverse transcription PCR, and in vitro inhibition‐based functional assays to explore the immunopathogenesis of Tregs in PV. Results Our results showed no statistically significant differences in total CD4+CD25+ cells and CD4+CD25high cells. In addition, expression levels of FOXP3 mRNA and the corresponding FOXP3 protein remained unchanged in the patients with PV and the HCs. However, the in vitro suppressive activity of CD4+CD25+ T cells was impaired in patients with PV compared with HCs. Conclusions Our observations suggest that inhibition of suppressive activity of Treg cells may be involved in the pathogenesis of PV.

Immunohistochemical expression of regulatory T cells (CD4+ CD25+ bright FOXP3+) in pemphigus patients

“…These findings are consistent with a recent study that found functional suppression of regulatory CD4 + CD25 + T cells in the peripheral blood of PV patients 19 . This suggests a problem with Tregs, either in terms of number or function.…”

“…mean values and percentage of skin lesional Tregs (CD 25 +, % CD 25 / CD4, Foxp 3 +, and % Foxp 3 / CD 4 ) in pemphigus patients compared with healthy controls and this result was in agreement with Xu et al, who found that Treg cells in pemphigus patients' blood measured by fluorescence-activated cell sorting were significantly fewer than in the control group, and also according to Sugiyama et al, the fraction of CD4+CD25+ Tregs among total CD4+ T cells in the blood ofPV patients was significantly lower than in controls, almost 10-fold lower 17,18. These findings are consistent with a recent study that found functional suppression of regulatory CD4 + CD25 + T cells in the peripheral blood of PV patients 19. This suggests a problem with Tregs, either in terms of number or function Terras et al (2014) 20 ,.…”

Short- and Long-Lived Autoantibody-Secreting Cells in Autoimmune Neurological Disorders

“…Conversely, in MG mediated by predominantly IgG1 autoantibodies against AChR, patients have been shown to harbor dysfunctional Tregs (95), and further, induction of Tregs via GM-CSF effectively suppressed experimental autoimmune MG (96). In pemphigus vulgaris (PV) mediated by predominantly IgG4 autoantibodies against desmoglein, contradicting data that Tregs have both not been able to suppress (97) and have suppressed autoimmune responses (98) are reported. These results underline the need for further investigations into the role of Tregs in autoantibodymediated autoimmunity.…”

El papel de las células T en la inmunopatogénesis del pénfigo vulgar

“…Por otro lado, Su et al 40 no encontraron diferencia en los niveles de nTreg periféricas entre sujetos con PV y controles sanos, aunque observaron que la capacidad supresora de estas células estaba disminuida.…”