The contribution of neuropilin‐1 in the stability of CD4+CD25+ regulatory T cells through the TGF‐β1/Smads signaling pathway in the presence of lipopolysaccharides

Abstract

Abstract Introduction This study investigates the synergistic effect of TGF‐β1 and Nrp‐1 on CD4+CD25+ Tregs' stabilization, and the associated pathways of signal transduction, in vitro models in the presence of LPS. Materials and Methods Spleen CD4+CD25+ Tregs cells of mice models in the presence of LPS, were transfected with an shRNA targeting Nrp‐1, Smad2, or Smad3, may or may not be treated with recombinant TGF‐β1. Followed by subsequent determination of cellular proliferation, rate of apoptosis, observation of the Foxp3, CTLA‐4, and TGF‐β1m+ expression levels, foxp3‐TSDR methylation, secretion levels of the inhibitory cytokines IL‐10 and TGF‐β1, and Smad2/3 of CD4+CD25+ Tregs expression. Results A remarkable stimulation in CD4+CD25+ Tregs' stability is noted after administering recombinant TGF‐β1 in the presence of LPS, and promoted cellular viability, increased Foxp3, CTLA‐4, and TGF‐β1m+ expression, and elevated secretion of IL‐10 and TGF‐β1. This also inhibited the apoptosis and methylation of foxp3‐ TSDR of CD4+CD25+ Tregs. The shRNA transfection silenced Nrp‐1 and Smad3, but not Smad2, resulting in the suppression of the recombinant TGF‐β1‐mediated effects in the presence of LPS. Conclusions According to the results, Nrp‐1 mediates TGF‐β1 to improve the stability of regulatory CD4+CD25+ T cells and maybe a possible therapeutic target with the ability to improve the CD4+CD25+ Tregs associated negative immunoregulation that is related to the TGF‐β1/Smads cell signaling during sepsis.

Keywords

• lipopolysaccharides
• negative immunoregulation
• neuropilin‐1
• regulatory T cells
• Sepsis
• transforming growth factor‐β1