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

// Yu-Lei Gao 1, * , Mu-Ming Yu 1, * , Song-Tao Shou 1, * , Ying Yao 1 , Yan-Cun Liu 1 , Li-Jun Wang 1 , Bin Lu 1 , Yan-Fen Chai 1 1 Department 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: chaiyanfen2012@126.com Yu-Lei Gao, email: gaoyulei828@126.com 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 high CD4 + 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 high CD4 + 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 high CD4 + CD25 + Tregs to conventional CD4 + CD25 - T cells. Tuftsin markedly inhibited the demethylation of Foxp3-Tregs specific demethylated region (TSDR) of Nrp-1 high CD4 + 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.