MyD88-dependent pathway in T cells directly modulates the expansion of colitogenic CD4+ T cells in chronic colitis

被引:51
作者
Tomita, Takayuki [1 ]
Kanai, Takanori [1 ]
Fujii, Toshimitsu [1 ]
Nemoto, Yasuhiro [1 ]
Okamoto, Ryuichi [1 ]
Tsuchiya, Kiichiro [1 ]
Totsuka, Teruji [1 ]
Sakamoto, Naoya [1 ]
Akira, Shizuo [2 ]
Watanabe, Mamoru [1 ]
机构
[1] Tokyo Med & Dent Univ, Grad Sch, Dept Gastroenterol & Hepatol, Bunkyo Ku, Tokyo 1138519, Japan
[2] Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan
关键词
D O I
10.4049/jimmunol.180.8.5291
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
TLRs that mediate the recognition of pathogen-associated molecular patterns are widely expressed on/in cells of the innate immune system. However, recent findings demonstrate that certain TLRs are also expressed in conventional TCR alpha beta(+) T cells that are critically involved in the acquired immune system, suggesting that TLR ligands can directly modulate T cell function in addition to various innate immune cells. In this study, we report that in a murine model of chronic colitis induced in RAG-2(-/-) mice by adoptive transfer of CD4(+)CD45RB(high) T cells, both CD4(+)CD45RB(high) donor cells and the expanding colitogenic lamina propria CD4(+)CD44RB(high) memory cells expresses a wide variety of TLRs along with MyD88, a key adaptor molecule required for signal transduction through TLRs. Although RAG-2(-/-) mice transferred with MyD88(-/-)CD(4+)CD45RB(high) cells developed colitis, the severity was reduced with the delayed kinetics of clinical course, and the expansion of colitogenic CD4(+) T cells was significantly impaired as compared with control mice transferred with MyD88(+/+)CD4(+)CD45RB(high) cells. When RAG-2(-/-) mice were transferred with the same number of MyD88(+/+) (Ly5.1(+)) and MyD88(-/-) (Ly5.2(+)) CD4(+)CD45RB(high) cells, MyD88(-/-)CD4(+) T cells showed significantly lower proliferative responses assessed by in vivo CFSE division assay, and also lower expression of antiapoptotic Bcl-2/Bcl-x(L) molecules and less production of IFN-gamma and IL-17, compared with the paired MyD88(+/+)CD4(+) T cells. Collectively, the MyD88-dependent pathway that controls TLR signaling in T cells may directly promote the proliferation and survival of colitogenic CD4+ T cells to sustain chronic colitis.
引用
收藏
页码:5291 / 5299
页数:9
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