SH2 domain–containing adaptor protein B expressed in dendritic cells is involved in T-cell homeostasis by regulating dendritic cell–mediated Th2 immunity
Clinical and Experimental Vaccine Research
;
: 50-60, 2017.
Article
in English
| WPRIM
| ID: wpr-43944
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 ANDMETHODS:
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phenotype
/
Dendritic Cells
/
T-Lymphocytes
/
Cytokines
/
Gene Silencing
/
Dermatitis, Atopic
/
Homeostasis
Limits:
Animals
Language:
English
Journal:
Clinical and Experimental Vaccine Research
Year:
2017
Type:
Article
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