SH2 domain-containing adaptor protein B expressed in dendritic cells is involved in T-cell homeostasis by regulating dendritic cell-mediated Th2 immunity.

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 . 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 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) BMDCs in a mouse atopic dermatitis model.

Results: SHB was steadily expressed in mouse splenic DCs and in -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 increased the expression of MHC class II and costimulatory molecules without affecting the cytokine expression of BMDCs. When co-cultured with T cells, SHB 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 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 by regulating DC-mediated Th2 polarization.