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

Takayuki Tomita, Takanori Kanai, Toshimitsu Fujii, Yasuhiro Nemoto, Ryuichi Okamoto, Kiichiro Tsuchiya, Teruji Totsuka, Naoya Sakamoto, Shizuo Akira, Mamoru Watanabe

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48 Citations (Scopus)

Abstract

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 TCRαβ+ 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+CD45RBhigh T cells, both CD4+CD45RBhigh donor cells and the expanding colitogenic lamina propria CD4+CD44hlgh 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-/-CD4+CD45RBhigh 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 +CD45RBhigh cells. When RAG-2-/- mice were transferred with the same number of MyD88+/+ (Ly5.1+) and MyDSS-/- (Ly5.2+) CD4+CD45RBhigh 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-xL molecules and less production of IFN-γ 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. The Journal of Immunology, 2008, 180:

Original languageEnglish
Pages (from-to)5291-5299
Number of pages9
JournalJournal of Immunology
Volume180
Issue number8
DOIs
Publication statusPublished - 2008 Apr 15
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Tomita, T., Kanai, T., Fujii, T., Nemoto, Y., Okamoto, R., Tsuchiya, K., Totsuka, T., Sakamoto, N., Akira, S., & Watanabe, M. (2008). MyD88-dependent pathway in T cells directly modulates the expansion of colitogenic CD4+ T cells in chronic colitis. Journal of Immunology, 180(8), 5291-5299. https://doi.org/10.4049/jimmunol.180.8.5291