Skin-homing CD4+ Foxp3+ T cells exert Th2-like function after staphylococcal superantigen stimulation in atopic dermatitis patients

P>Background The effect of staphylococcal superantigens (SsAgs) on cutaneous lymphocyte-associated antigen (CLA)+ CD4+ Foxp3+ T cells of atopic dermatitis (AD) patients is unknown. Objective To compare the effects of SsAgs on the ratio, function, and apoptosis of CCR6+ subtype and CCR6- subtype of CLA+ CD4+ Foxp3+ T cells among AD patients, asthma/allergic rhinitis (AR) patients without AD, and healthy subjects. Methods Using immunofluorescence staining followed by flow cytometric analysis, we analysed peripheral blood mononuclear cells cultured with or without staphylococcal enterotoxin B (SEB) stimulation in 20 AD patients, 20 asthma/AR patients without AD, and 20 healthy subjects. Results SEB decreased CCR6+/CCR6- ratio in CLA+ CD4+ Foxp3+ T cells from AD patients and increased CCR6+/CCR6- ratio in those from healthy subjects. SEB induced the production of type 2 T helper cell (Th2) cytokine interleukin (IL)-5 in CCR6- subtype and anti-inflammatory cytokine IL-10 in CCR6+ subtype of CLA+ CD4+ Foxp3+ T cells. CLA+ CD4+ Foxp3+ T cells from AD patients produced more IL-5 and less IL-10 after SEB stimulation than those from healthy subjects. CCR6- subtype of CLA+ CD4+ Foxp3+ T cells from AD patients and CCR6+ subtype of those cells from healthy subjects were more resistant to SEB-induced caspase-3 activation than the other subtype and those from other subjects. Conclusions and Clinical Relevance Despite a phenotype of regulatory T cells, skin-homing CD4+ Foxp3+ T cells of AD patients exert effector Th2-like function after SsAgs stimulation, which may aggravate allergic skin inflammation.