title: CISH is induced during DC development and regulates DC-mediated CTL activation.
abstract: The cytokine inducible SH2-domain protein (CISH) is a well-known STAT5 target gene, but its role in the immune system remains uncertain. In this study, we found that CISH is predominantly induced during dendritic cell (DC) development from mouse bone marrow (BM) cells and plays a crucial role in type 1 DC development and DC-mediated CTL activation. CISH knockdown reduced the expression of MHC class I, co-stimulatory molecules and pro-inflammatory cytokines in BMDCs. Meanwhile, the DC yield was markedly enhanced by CISH knockdown via cell-cycle activation and reduction of cell apoptosis. Down-regulation of cell proliferation at the later stage of DC development was found to be associated with CISH-mediated negative feedback regulation of STAT5 activation. In T-cell immunity, OT-1 T-cell proliferation was significantly reduced by CISH knockdown in DCs, whereas OT-2 T-cell proliferation was not affected by CISH knockdown. CTLs generated by DC vaccination were also markedly reduced by CISH knockdown, followed by significant impairment of DC-based tumor immunotherapy. Taken together, our data suggest that CISH expression at the later stage of DC development triggers the shutdown of DC progenitor cell proliferation and facilitates DC differentiation into a potent stimulator of CTLs.
authors: Department of Biological Sciences, Sungkyunkwan University, Suwon, Gyeonggi-do, South Korea.
authors: Mohammad Alam
authors: MA
authors: Miah
authors: Cheol-Hee
authors: CH
authors: Yoon
authors: Joonoh
authors: J
authors: Kim
authors: Jinah
authors: J
authors: Jang
authors: Young-Rim
authors: YR
authors: Seong
authors: Yong-Soo
authors: YS
authors: Bae
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000494:pharmacology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000494:pharmacology; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015395:Histocompatibility Antigens Class I; D034741:RNA, Small Interfering; D050826:Suppressor of Cytokine Signaling Proteins