Interleukin-5 induces apoptotic defects in CD4+ T cells of patients with allergic rhinitis.

Abstract

T helper (Th)2 polarization plays an important role in the pathogenesis of allergic diseases; the underlying mechanism remains to be further investigated. B cell lymphoma protein-2 like protein-12 (Bcl2L12) has the anti-apoptotic function. This study aims to elucidate the contribution of Bcl2L12 to Th2 polarization in patients with allergic rhinitis (AR). In this study, human CD4+ T cells were isolated from blood samples collected from AR patients and healthy control (HC) subjects. The immune response profiles of CD4+ T cells were analyzed by immunologic approaches. The results showed that AR CD4+ T cells (CD4+ T cells collected from AR patients) showed defects of apoptosis. The expression of FasL in AR CD4+ T cells was lower than that of HC CD4+ T cells. Serum IL-5 levels were negatively correlated with the expression of FasL in AR CD4+ T cells. Exposure of CD4+ T cells to IL-5 in the culture suppressed the expression of FasL and increased the expression of Bcl2L12. IL-5 increased the levels of Bcl2L12 in CD4+ T cells, the latter bound to the FasL promoter to prevent FasL gene transcription. Inhibition of Bcl2L12 restored the apoptosis machinery in AR CD4+ T cells. In conclusion, overexpression of Bcl2L12 in CD4+ T cells compromises the apoptosis machinery; the latter can be restored by inhibition of Bcl2L12. BcL2L12 in CD4+ T cells may be a novel target for the treatment of AR and other allergic disorders.