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KMID : 1039120170060010050
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Clinical and Experimental Vaccine Research
2017 Volume.6 No. 1 p.50 ~ p.60
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SH2 domain?containing adaptor protein B expressed in dendritic cells is involved in T-cell homeostasis by regulating dendritic cell?mediated Th2 immunity
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Ahmed Md. Selim
Kang Myeong-Ho
Lee Ezra
Park Yu-Jin
Jeong Yi-Deul
Bae Yong-Soo
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Abstract
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Purpose: The Src homology 2 domain?containing adaptor protein B (SHB) is widely expressed in immune cells and acts as an important regulator for hematopoietic cell function. SHB silencing induces Th2 immunity in mice. SHB is also involved in T-cell homeostasis in vivo. However, SHB has not yet been studied and addressed in association with dendritic cells (DCs).
Materials and Methods: The effects of SHB expression on the immunogenicity of DCs were assessed by Shb gene silencing in mouse bone marrow?derived DCs (BMDCs). After silencing, surface phenotype, cytokine expression profile, and T-cell stimulation capacity of BMDCs were examined. We investigated the signaling pathways involved in SHB expression during BMDC development. We also examined the immunogenicity of SHB-knockdown (SHBKD) BMDCs in a mouse atopic dermatitis model.
Results: SHB was steadily expressed in mouse splenic DCs and in in vitro?generated BMDCs in both immature and mature stages. SHB expression was contingent on activation of the mitogen- activated protein kinase/Foxa2 signaling pathway during DC development. SHBKD increased the expression of MHC class II and costimulatory molecules without affecting the cytokine expression of BMDCs. When co-cultured with T cells, SHBKD in BMDCs significantly induced CD4+ T-cell proliferation and the expression of Th2 cytokines, while the regulatory T cell (Treg) population was downregulated. In mouse atopic dermatitis model, mice inoculated with SHBKD DCs developed more severe symptoms of atopic dermatitis compared with mice injected with control DCs.
Conclusion: SHB expression in DCs plays an important role in T-cell homeostasis in vivo by regulating DC-mediated Th2 polarization.
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KEYWORD
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SHB, Dendritic cells, Th2 immunity, Atopic dermatitis
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