Survivin facilitates T‐helper 2–biased inflammation in the airway
Jin‐Mei Xue MD, PhD Mei‐Zhen Zhao PhD Fei Ma MD, PhD Shan‐Shan Li MSc Li‐Hua Mo MSc Xian‐Hai Zeng MD Yong‐Jin Wu MD Jiang‐Qi Liu MD Tian‐Yong Hu MSc Rui‐Di Xie MD … See all authors
First published: 04 February 2019 https://doi.org/10.1002/alr.22301
Funding sources for the study: National “13th‐5” Key Programme; Precision Medicine Research Project (2016YFC0905802 and 2016YFC0903700); Guangdong Provincial Scientific Technological Research Project (2016A020216029); and Shenzhen Scientific Technological Basic Research Project (JCYJ20160429114659119, JCYJ20160328144536436, and KQTD20170331145453160).
Potential conflict of interest: None provided.
J.M.X, M.Z.Z., and F.M. contributed equally to this work.
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Abstract
Background
The biased T helper 2 (Th2) responses play a critical role in the pathogenesis of allergy. The underlying mechanism is not fully understood yet. Survivin can regulate multiple cellular activities. This study aims to elucidate the role of survivin in the development and maintenance of Th2 polarization.
Methods
CD4+ T cells were isolated from blood samples collected from patients with allergic asthma (AS) and HS control (HS) subjects. Mice carrying CD4+ T cells with survivin knockout (KO mice) were employed to test the role of survivin in the development of the biased Th2 responses.
Results
KO mice failed to induce airway allergy. Peripheral CD4+ T cells expressed survivin, which was higher in the AS group than that in the HS group. Naive CD4+ T cells with higher expression of survivin were prone to differentiating into Th2 cells. Survivin bound to the Il4 promoter in CD4+ T cells to enhance Il4 gene transcription. The expression of Fas was lower in CD4+ T cells of the AS group than that in the HS group. Overexpression of survivin suppressed the expression of Fas and impaired the activation‐induced cell death (AICD) of CD4+ T cells.
Conclusion
Survivin facilitates the development of biased Th2 polarization through promoting expression of interleukin 4 (IL‐4) and impairing the AICD machinery of CD4+ T cells. To modulate the expression of survivin in CD4+ T cells has the translational potential in the treatment of allergic diseases.
Jin‐Mei Xue MD, PhD Mei‐Zhen Zhao PhD Fei Ma MD, PhD Shan‐Shan Li MSc Li‐Hua Mo MSc Xian‐Hai Zeng MD Yong‐Jin Wu MD Jiang‐Qi Liu MD Tian‐Yong Hu MSc Rui‐Di Xie MD … See all authors
First published: 04 February 2019 https://doi.org/10.1002/alr.22301
Funding sources for the study: National “13th‐5” Key Programme; Precision Medicine Research Project (2016YFC0905802 and 2016YFC0903700); Guangdong Provincial Scientific Technological Research Project (2016A020216029); and Shenzhen Scientific Technological Basic Research Project (JCYJ20160429114659119, JCYJ20160328144536436, and KQTD20170331145453160).
Potential conflict of interest: None provided.
J.M.X, M.Z.Z., and F.M. contributed equally to this work.
Read the full text
ePDFPDFTOOLS SHARE
Abstract
Background
The biased T helper 2 (Th2) responses play a critical role in the pathogenesis of allergy. The underlying mechanism is not fully understood yet. Survivin can regulate multiple cellular activities. This study aims to elucidate the role of survivin in the development and maintenance of Th2 polarization.
Methods
CD4+ T cells were isolated from blood samples collected from patients with allergic asthma (AS) and HS control (HS) subjects. Mice carrying CD4+ T cells with survivin knockout (KO mice) were employed to test the role of survivin in the development of the biased Th2 responses.
Results
KO mice failed to induce airway allergy. Peripheral CD4+ T cells expressed survivin, which was higher in the AS group than that in the HS group. Naive CD4+ T cells with higher expression of survivin were prone to differentiating into Th2 cells. Survivin bound to the Il4 promoter in CD4+ T cells to enhance Il4 gene transcription. The expression of Fas was lower in CD4+ T cells of the AS group than that in the HS group. Overexpression of survivin suppressed the expression of Fas and impaired the activation‐induced cell death (AICD) of CD4+ T cells.
Conclusion
Survivin facilitates the development of biased Th2 polarization through promoting expression of interleukin 4 (IL‐4) and impairing the AICD machinery of CD4+ T cells. To modulate the expression of survivin in CD4+ T cells has the translational potential in the treatment of allergic diseases.
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