The mechanisms of soluble CD83 in promoting proliferation ability of tolerant DCs and T reg cells and in sustaining immune tolerance status
10.19405/j.cnki.issn1000-1492.2023.08.009
- Author:
Qifeng Song
1
;
Lianghui Gao
1
;
Wang Li
1
;
Yizhong Zhang
1
Author Information
1. Dept of Hepatobiliary and Pancreatic Surgery, The First Afiliated Hospital of Hainan Medical College , Haikou 570100
- Publication Type:Journal Article
- Keywords:
immunosuppressive agent;
soluble CD83;
tolerant DCs;
Treg cells;
RelB;
indoleamine 2 ,3 ⁃dioxygenase
- From:
Acta Universitatis Medicinalis Anhui
2023;58(8):1300-1305,1312
- CountryChina
- Language:Chinese
-
Abstract:
Objective :To explore the molecular mechanisms of immunosuppressive activity of soluble CD83 (sCD83) .
Methods :Bone marrow⁃derived dendritic cells ( DCs) and CD4 + T cells in the spleen were isolated from bone marrow progenitor cells of 6 - 8 ⁃week⁃old C57B/6 mice. DCs and CD4 + T cells were treated with 10 μl
PBS (Control group) or 10 μl 10 μg/ml soluble CD83 (sCD83 group) , respectively. Immature DCs (imDCs) in DCs and CD4 + CD25 + FOXP3 + T cells (Treg cells) in CD4 + T cells were determined by flow cytometry. Western blot was used to determine the expression levels of indoleamine 2 ,3 ⁃dioxygenase (IDO) in imDCs and the expression levels of phosphatase and tensin homolog (PTEN) , phosphorylated⁃Akt serine/threonine kinase 1 ( p⁃Akt) , Akt , nucleus NF⁃κB subunit (RelB) , cytoplasm RelB and programmed cell death 1 ( PD⁃1) in Treg cells. ELISA was used to determine the level of kynurenine in DCs culture supernatant , and the levels of interleukin⁃10 ( IL⁃10) , transforming growth factor⁃β (TGF⁃ β) and IL⁃12 in imDCs and CD4 + T cells co⁃culture system.
Results:Compared with Control group , the percentage of DCs cell counts expressing the surface markers of CD40 , CD83 , CD86 and major histocompatibility complex class⁃ Ⅱ (MHC Ⅱ ) in sCD83 group decreased (P < 0. 05) , with the level of kynurenine in DCs culture supernatant increased (P < 0. 05) . Compared with Control group , the percentage of Treg cell counts in sCD83 group increased ( P < 0. 05) , with the expression levels of PTEN and cytoplasm RelB enhanced (P < 0. 05) , while the expression levels of p⁃Akt , nucleus RelB and PD⁃1 decreased (P < 0. 05) . There was no significant difference in the expression level of Akt between the two groups. In the imDCs and CD4 +T cells co⁃cultured supernatants , compared with Control group , the levels of IL⁃10 and TGF⁃ β increased , and the level of IL⁃12 decreased in sCD83 group (P < 0. 05) .
Conclusion : sCD83 can inhibit CD4 + T cells nucleus RelB levels and regulate cytokines secretion so as to have an effects on cellular crosstalk of imDCs and Treg cells and promote imDCs and Treg cells proliferation.
- Full text:2024081610514892978可溶性CD83促进耐受性D...胞增殖和免疫耐受的分子机制_宋奇锋 (1).pdf