Bcl2L12 Contributes to Th2-Biased Inflammation in the Intestinal Mucosa by Regulating CD4+ T Cell Activities

Abstract

The Th2-biased inflammation and immune deregulation play a critical role in the pathogenesis of ulcerative colitis (UC). Recent studies indicate that the Bcl2-like protein 12 (Bcl2L12) is associated with immune deregulation of UC. This study aims to investigate the role of Bcl2L12 in the induction of aberrant Th2-biased inflammation. In this study, peripheral blood samples were collected from patients with inflammatory bowel disease. The Th2 cell activities were analyzed by flow cytometry, real-time quantitative RT-PCR, and Western blotting. Mice with Bcl2L12-knockout CD4 T cells were used in the experiments. The results showed that the expression of Bcl2L12 was detected in peripheral CD4 T cells, which was significantly higher in UC patients than in healthy subjects. A positive correlation between the expression of Bcl2L12 and Th2 cytokines was detected in CD4 T cells from UC patients. Naive CD4 T cells with Bcl2L12 overexpression were prone to differentiate into Th2 cells. Mice with Bcl2L12 deficiency failed to induce the Th2-biased inflammation in the intestine. Bcl2L12 bound GATA3 to form a complex to enhance the binding between GATA3 and the promoter to enhance the expression of IL-4 in CD4 T cells. CD4 T cells with Bcl2L12 overexpression were resistant to apoptosis. In conclusion, the Bcl2L12 is a critical factor in the induction of aberrant Th2 polarization by upregulating Th2 responses and downregulating Th2 cell apoptosis. Bcl2L12 may be a novel therapeutic target in the management of the disorders with Th2-biased inflammation.

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

“…It was lately found that Bcl2L12 was also involved in the development of other types of cancer with its anti‐apoptotic activities . Further reports indicate that Bcl2L12 is associated with the immune deregulation . The present study has added novel information to this study field that Bcl2L12 regulates CD4 + T cell activities by compromising the apoptosis machinery to induce defects of apoptosis in CD4 + T cells.…”

“…20 Further reports indicate that Bcl2L12 is associated with the immune deregulation. 12,13 The present study has added novel information to this study field that Bcl2L12 regulates CD4 + T cell activities by compromising the apoptosis machinery to induce defects of apoptosis in CD4 + T cells. On the other hand, the defects of apoptosis in CD4 + T cells may be also a result of Th2 polarization because IL-5 can increase the expression of Bcl2L12 in CD4 + T cells.…”

“…The phenomenon implies the expression and functions of some regulatory factors of apoptosis in CD4 + T cells may be unusually changed. Our recent studies revealed that Bcl2‐like protein‐12 (Bcl2L12) was aberrantly higher in patients with AR and patients with intestinal inflammation . Bcl2L12 is an anti‐apoptosis protein .…”

“…Our recent studies revealed that Bcl2-like protein-12 (Bcl2L12) was aberrantly higher in patients with AR 12 and patients with intestinal inflammation. 13,14 Bcl2L12 is an anti-apoptosis protein. 15 Whether Bcl2L12 is involved in impairing the apoptotic machinery and contributes to the development of Th2 polarization in AR is to be determined.…”

Soluble CD83 alleviates experimental allergic rhinitis through modulating antigen-specific Th2 cell property

“…Our previous studies indicate that Bcl2L12 plays a critical role in the pathogenesis of Th2 polarization [17]. We wondered if the low serum sCD83 levels were also associated with the over expression of Bcl2L12 in sTh2 cells.…”