Toll-like receptor 2 suppresses Toll-like receptor 9 responses in Peyer's patch dendritic cells

作者：Kotaki Ryutaro; Wajima Shun ichi; Shiokawa Aya; Hachimura Satoshi^*

来源：Immunobiology, 2015, 220(6): 734-743.

DOI：10.1016/j.imbio.2014.12.022

• Dendritic cells
• Interleukin-12
• Interleukin-23
• Intestinal immunity
• Peyer's patches
• Toll-like receptors

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.

• 出版日期2015-6