SH2 domain–containing adaptor protein B expressed in dendritic cells is involved in T-cell homeostasis by regulating dendritic cell–mediated Th2 immunity.
- Author:
Md Selim AHMED
1
;
Myeong Ho KANG
;
Ezra LEE
;
Yujin PARK
;
Yideul JEONG
;
Yong Soo BAE
Author Information
- Publication Type:Original Article
- Keywords: SHB; Dendritic cells; Th2 immunity; Atopic dermatitis
- MeSH: Animals; Cytokines; Dendritic Cells*; Dermatitis, Atopic; Gene Silencing; Homeostasis*; Mice; Phenotype; T-Lymphocytes*
- From:Clinical and Experimental Vaccine Research 2017;6(1):50-60
- CountryRepublic of Korea
- Language:English
- Abstract: 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 (SHB(KD)) 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. SHB(KD) increased the expression of MHC class II and costimulatory molecules without affecting the cytokine expression of BMDCs. When co-cultured with T cells, SHB(KD) 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 SHB(KD) 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.
