Archive | 2021
Effect of BDNF on Differentiation of Circulating Th17 and Treg Cells in SLE Patients and Exploration of Signal Transduction Pathways
Abstract
\n Circulating brain-derived neurotrophic factor(BDNF) is mainly derived from lymphocytes. The serum BDNF level in SLE is decreased, and BDNF may be involved in the pathogenesis of systemic lupus erythematosus(SLE). Our aim is to determine whether BDNF affects the differentiation of CD4+T cells into regulatory T(Treg) or T helper 17(Th17). 30 patients were selected. TGF-β and IL-6 were added to induce differentiation of Treg and Th17. After co-cultured with BDNF, the percentages of CD4+CD25+CD127low and CD4+IL-17A+ were detected by Flow cytometry, and the expression of Foxp3mRNA and RORγtmRNA were detected by Rt-PCR. Under the condition of Th17 and Treg polarization, after co-cultured with BDNF and TrkB IgG, the phosphorylation of Akt, mTORC1 and ERK1/2 were detected by western-blot, the percentages of CD4+CD25+CD127low and CD4+IL-17A+ were detected by Flow cytometry. Under the condition of Th17 polarization, with the increase of BDNF concentration(60ng/ml, 120ng/ml, 350ng/ml), the percentages of CD4+IL-17A+ and the expression of RORγtmRNA were decreased(p<0.01; p<0.001). Under the condition of Treg polarization, the percentages of CD4+CD25+CD127low and the expression of Foxp3mRNA were increased(p<0.001). Regardless of Th17 or Treg polarization, the phosphorylation of Akt, mTORC1 and ERK1/2 in the BDNF group were reduced(p<0.001), and the phosphorylation of Akt, mTORC1 in the TrkBIgG group were enhanced(p<0.001). BDNF down-regulates the differentiation of Th17 and promotes the differentiation of Treg in SLE through inhibiting the activation of PI3K-Akt-mTORC1 axis and ERK1/2 pathway. BDNF could play a certain role in maintaining the balance of Treg/Th17 ratio in SLE.