title: Toll-like receptor 2 suppresses Toll-like receptor 9 responses in Peyer's patch dendritic cells.
abstract: 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.
authors: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
authors: Ryutaro
authors: R
authors: Kotaki
authors: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
authors: Shun-ichi
authors: S
authors: Wajima
authors: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
authors: Aya
authors: A
authors: Shiokawa
authors: Research Center for Food Safety, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan. Electronic address: ahachi@mail.ecc.u-tokyo.ac.jp.
authors: Satoshi
authors: S
authors: Hachimura
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D008024:Ligands; D051379:Mice; D018345:Mice, Knockout; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D010581:Peyer's Patches / Q000276:immunology* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051194:Toll-Like Receptor 1 / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism*
chemical_list: D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051217:Toll-Like Receptor 9
keywords: Dendritic cells; Interleukin-12; Interleukin-23; Intestinal immunity; Peyer's patches; Toll-like receptors