Achievements

Hepatic IL-7 regulates T cell responses in vivo.

Infections induce TLR-mediated signals in a variety of inflammatory cells, which, in response, produce proinflammatory cytokines. These cytokines initiate various systemic responses and “acute-phase reactions,” a constellation of processes characterized by altered protein expression profiles in hepatocytes. On the other hand, the production of IL-7 in stromal cells is reported to occur at a constant rate in vivo, unaffected by most extrinsic stimuli. IL-7 signaling, which appears to limit the size of the lymphocyte pool, instead is thought to be regulated by IL-7 receptor α-mediated IL-7 consumption rather than the rate of IL-7 expression. Here we show that IL-7 is a hepatically expressed protein that directly controls T cell responses. Inhibiting IL-7 expression in the liver abrogated several TLR-mediated T cell events, including enhanced CD4+ T cell and CD8+ T cell survival, augmented CD8+ T cell cytotoxic activity, and the development of experimental autoimmune encephalitis, a Th17 cell-mediated autoimmune disease. Thus, T cell responses are regulated by hepatocyte-derived IL-7, which is expressed in response to TLR signaling in vivo. TLR-induced IL-7 expression in the liver is an acute-phase response that may be a good diagnostic and therapeutic target for conditions characterized by TLR-mediated T cell dysregulation, including autoimmune diseases, and may facilitate efficient vaccine development.

Hepatic interleukin-7 expression regulates T cell responses.

Sawa Y., Y. Arima, H. Ogura, C. Kitabayashi, J-J Jiang, T. Fukushima, D. Kamimura, T. Hirano, and M. Murakami.
Immunity. 2009 Mar;30(3):447-57. 2009 (PubMed)

ADDRESS

Achievements

Hepatic IL-7 regulates T cell responses in vivo.