First Author | Kotaki R | Year | 2015 |
Journal | Immunobiology | Volume | 220 |
Issue | 6 | Pages | 734-43 |
PubMed ID | 25638261 | Mgi Jnum | J:347942 |
Mgi Id | MGI:6877942 | Doi | 10.1016/j.imbio.2014.12.022 |
Citation | Kotaki R, et al. (2015) Toll-like receptor 2 suppresses Toll-like receptor 9 responses in Peyer's patch dendritic cells. Immunobiology 220(6):734-43 |
abstractText | In the intestine, immune responses to commensal microbes should be regulated precisely. This regulation is achieved partly by dendritic cells (DCs), which recognize microbes through Toll-like receptors (TLRs). Although TLR responses have been intensely studied, cross-talk between individual TLRs remains unclear. The present study shows that TLR2 suppressed TLR9-induced Il12b gene expression and subsequent interleukin (IL)-12 and IL-23 production in DCs from Peyer's patch, a lymphoid tissue in the small intestine. The DCs expressed Il12b gene and produced IL-12 and IL-23 in response to TLR9 stimulation, and these responses were suppressed when the DCs were stimulated simultaneously with TLR2. The suppression was also observed in the non-intestinal DCs, such as spleen DCs and bone marrow-derived DCs. Peyer's patch DCs expressed Il12b gene also in response to TLR7 or CD40 stimulation, but these responses were not suppressed by simultaneous TLR2 stimulation. In addition, TLR9-induced Tnf and Il6 gene expression was not suppressed by TLR2. Furthermore, the supernatant of TLR2-stimulated DCs could not suppress TLR9-induced Il12b gene expression. These results suggest that TLR2 suppress TLR9-induced responses selectively, and this suppression is not mediated by secretory factors. The suppressive TLR cross-talk might play a certain role in preventing excess inflammatory responses to commensal microbes in the intestine and may have implications for the therapeutic strategies for intestinal inflammatory diseases, autoimmune diseases and cancer. |