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Publication : Toll like Receptor 2 engagement on CD4<sup>+</sup> T cells promotes TH9 differentiation and function.

First Author  Karim AF Year  2017
Journal  Eur J Immunol Volume  47
Issue  9 Pages  1513-1524
PubMed ID  28665005 Mgi Jnum  J:246487
Mgi Id  MGI:5922947 Doi  10.1002/eji.201646846
Citation  Karim AF, et al. (2017) Toll like Receptor 2 engagement on CD4+ T cells promotes TH9 differentiation and function. Eur J Immunol 47(9):1513-1524
abstractText  We have recently demonstrated that mycobacterial ligands engage Toll like receptor 2 (TLR2) on CD4+ T cells and up-regulate T-cell receptor (TCR) triggered Th1 responses in vitro and in vivo. To better understand the role of T-cell expressed TLR2 on CD4+ T-cell differentiation and function, we conducted a gene expression analysis of murine naive CD4+ T-cells stimulated in the presence or absence of TLR2 co-stimulation. Unexpectedly, naive CD4+ T-cells co-stimulated via TLR2 showed a significant up-regulation of Il9 mRNA compared to cells co-stimulated via CD28. Under TH9 differentiation, we observed up-regulation of TH9 differentiation, evidenced by increases in both percent of IL-9 secreting cells and IL-9 in culture supernatants in the presence of TLR2 agonist both in polyclonal and Ag85B cognate peptide specific stimulations. Under non-polarizing conditions, TLR2 engagement on CD4+ T-cells had minimal effect on IL-9 secretion and TH9 differentiation, likely due to a prominent effect of TLR2 signaling on IFN-gamma secretion and TH1 differentiation. We also report that, TLR2 signaling in CD4+ T cells increased expression of transcription factors BATF and PU.1, known to positively regulate TH9 differentiation. These results reveal a novel role of T-cell expressed TLR2 in enhancing the differentiation and function of TH9 T cells.
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