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.

• Authors: Xiang-Qian Luo, Fei Ma, Shuai Wang, Mei-Zhen Zhao, Jian-Bo Shao, Xiao-Rui Geng, Jiang-Qi Liu, Li-Hua Mo, Li Guan, Zhi-Gang Liu, Da-Bo Liu, Ping-Chang Yang
• Journal: Journal of leukocyte biology (J Leukoc Biol) Vol. 105 Issue 4 Pg. 719-727 (04 2019) ISSN: 1938-3673 [Electronic] England
• PMID: 30694585 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2019 Society for Leukocyte Biology.

Chemical References

• BCL2L12 protein, human
• Fas Ligand Protein
• Interleukin-5
• Muscle Proteins
• Proto-Oncogene Proteins c-bcl-2
• RNA, Messenger

Topics

• Adult
• Apoptosis
• CD4-Positive T-Lymphocytes (immunology)
• Fas Ligand Protein (genetics, metabolism)
• Female
• Humans
• Interleukin-5 (blood, metabolism)
• Male
• Muscle Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• RNA, Messenger (genetics, metabolism)
• Rhinitis, Allergic (blood, genetics, immunology, pathology)
• Transcription, Genetic