Tuftsin prevents the negative immunoregulation of neuropilin-1 high CD4 + CD25 + Regulatory T cells and improves survival rate in septic mice

Yu-Lei Gao; Mu-Ming Yu; Song-Tao Shou; Ying Yao; Yan-Cun Liu; Li-Jun Wang; Bin Lu; Yan-Fen Chai

doi:10.18632/oncotarget.13235

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Tuftsin prevents the negative immunoregulation of neuropilin-1^highCD4⁺CD25⁺Regulatory T cells and improves survival rate in septic mice

Yu-Lei Gao _, Mu-Ming Yu, Song-Tao Shou, Ying Yao, Yan-Cun Liu, Li-Jun Wang, Bin Lu and Yan-Fen Chai

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Oncotarget. 2016; 7:81791-81805. https://doi.org/10.18632/oncotarget.13235

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Abstract

Yu-Lei Gao1,*, Mu-Ming Yu1,*, Song-Tao Shou1,*, Ying Yao1, Yan-Cun Liu1, Li-Jun Wang1, Bin Lu1, Yan-Fen Chai1

1Department of Emergency Medicine, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China

*These authors have contributed equally to this work

Correspondence to:

Yan-Fen Chai, email: [email protected]

Yu-Lei Gao, email: [email protected]

Keywords: sepsis, regulatory T cells, negative immunoregulation, tuftsin, neuropilin-1

Received: June 29, 2016 Accepted: October 28, 2016 Published: November 09, 2016

ABSTRACT

Our previous research showed that neuropilin (Nrp) -1^highCD4⁺CD25⁺Regulatory T cells (Tregs) exhibited primary negative immunoregulation in sepsis induced immune dysfunction. Tuftsin is the typical ligand of Nrp-1. Herein, we investigated the potential therapeutic value and mechanisms of tuftsin in sepsis. Sepsis per se markedly decreased the serum concentration of tuftsin, administration of tuftsin improved the survival rate of septic mice with cecal ligation and puncture (CLP). In vitro study, tuftsin prevented the negative immunoregulation of Nrp-1^highCD4⁺CD25⁺Tregs, including weakening the expression of forkhead/winged helix transcription factor (Foxp)- 3/cytotoxic T lymphocyte associated antigen (CTLA)-4, inhibiting the secretion of transforming growth factor (TGF)-β, and weakening the immunosuppressive function of Nrp-1^highCD4⁺CD25⁺Tregs to conventional CD4⁺CD25^-T cells. Tuftsin markedly inhibited the demethylation of Foxp3-Tregs specific demethylated region (TSDR) of Nrp-1^highCD4⁺CD25⁺Tregs. Tuftsin could represent a new potential therapeutic agentia to improve the outcome of septic mice, and associate with preventing the negative immunoregulation of Tregs via Nrp-1.

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Tuftsin prevents the negative immunoregulation of neuropilin-1highCD4+CD25+Regulatory T cells and improves survival rate in septic mice

Abstract

Tuftsin prevents the negative immunoregulation of neuropilin-1^highCD4⁺CD25⁺Regulatory T cells and improves survival rate in septic mice