SH2 domain-containing adaptor protein B expressed in dendritic cells is involved in T-cell homeostasis by regulating dendritic cell-mediated Th2 immunity.
OBJECTIVE
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 homeostasisin vivo. However, SHB has not yet been studied and addressed in association with dendritic cells (DCs).


METHODS
The effects of SHB expression on the immunogenicity of DCs were assessed byShbgene 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 inin 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. SHBKDincreased the expression of MHC class II and costimulatory molecules without affecting the cytokine expression of BMDCs. When co-cultured with T cells, SHBKDin 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 SHBKDDCs developed more severe symptoms of atopic dermatitis compared with mice injected with control DCs.


CONCLUSIONS
SHB expression in DCs plays an important role in T-cell homeostasisin vivoby regulating DC-mediated Th2 polarization.
Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
Md Selim
0000-0002-9601-8031
MS
Ahmed
Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
Myeong-Ho
0000-0001-5877-9916
MH
Kang
Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
Ezra
0000-0003-4508-9371
E
Lee
Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
Yujin
0000-0002-7696-4194
Y
Park
Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
Yideul
0000-0002-2667-9256
Y
Jeong
Department of Biological Science, Sungkyunkwan University, Suwon, Korea.
Yong-Soo
0000-0002-2233-9449
YS
Bae
Atopic dermatitis; Dendritic cells; SHB; Th2 immunity