Neuropilin-1 is a co-expression receptor for membrane associated transforming growth factor-βcontributing to the immunosuppressive property of rgulatory T cells / 中国中西医结合急救杂志

ABSTRACT

Objective To investigate the effect of co-expression of neuropilin-1(Nrp-1)and transforming growth factor-β(TGF-β)on regulatory T cell(Treg)-mediated immunosuppression. Methods CD4+CD25+Tregs were isolated from the spleens of male Balb/c mice. CD4+CD25+Tregs were blocked with various doses of Nrp-1 antibody(Ab-Nrp-1,0.5,5,10 μg/ml)for 24 hours with anti-CD3/CD28 and lipopolysaccharide(LPS)stimulation, and expression of Nrp-1 and TGF-βwas determined by flow cytometry. Meanwhile,CD4+CD25+Tregs were cultured with different doses of Ab-Nrp-1 for 1 hour,and co-cultured with CD4+CD25-T cell for 12,24 and 48 hours respectively,the proliferative activity of CD4+CD25-T cells was analyzed by microplate reader. Results Compared to control group,the expressions of Nrp-1 and TGF-β were significantly increased under anti-CD3/CD28 and LPS stimulation(both P<0.05),and treatment with Ab-Nrp-1 markedly inhibited the expression of TGF-β in a dose-dependent manner(P<0.05). The normal Treg had the potential to inhibit the proliferation of CD4+CD25-T cells(P<0.05),while various doses of Ab-Nrp-1 had the ability to reverse the immunosuppressive function of CD4+CD25+Treg in a dose-and time-dependent response manner,5μg/ml has the strongest ability,expecially after 24 hours. Conclusion Treg cell plays an important role in mediating immunosuppressive response via membrane associated TGF-β,and co-expression of Nrp-1 can markedly promote the immunosuppressive function.