The immune system uses a large number of proteins to sense the presence of microbes, including a family of proteins known as TLRs. The function of TLRs on immune cells known as DCs and macrophages has been well characterized, but the role of TLR4 on immune cells known as CD4+ T cells has not been determined.
However, José M. González-Navajas, Eyal Raz and colleagues, at the University of California at San Diego, La Jolla, have now determined that triggering TLR4 on CD4+ T cells dampens their inflammatory function, as TLR4 deficiency in two mouse models of colitis (inflammation of the intestines) accelerated the development of disease and/or induced more severe disease.
Further analysis identified a molecular signaling pathway underlying the inhibitory effects of TLR4 triggering on CD4+ T cell inflammatory function, providing insight into the regulation of CD4+ T cell responses.
The research appears in the Journal of Clinical Investigation.
- José M. González-Navajas, Sean Fine, Jason Law, Sandip K. Datta, Kim P. Nguyen, Mandy Yu, Maripat Corr, Kyoko Katakura, Lars Eckman, Jongdae Lee and Eyal Raz. TLR4 signaling in effector CD4 T cells regulates TCR activation and experimental colitis in mice. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI40055
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