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Immunity. 2009 Mar 20;30(3):447-57. doi: 10.1016/j.immuni.2009.01.007. Epub 2009 Mar 12.

Hepatic interleukin-7 expression regulates T cell responses.

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Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan.


Systemic cytokine activity in response to Toll-like receptor (TLR) signaling induces the expression of various proteins in the liver after infections. Here we show that Interleukin-7 (IL-7), the production of which was thought to occur at a constant rate in vivo, was a hepatically expressed protein that directly controled T cell responses. Depletion of 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. We suggested that TLR-induced IL-7 expression in the liver, which is an acute-phase response, may be a good diagnostic and therapeutic target for efficient vaccine developments and for conditions characterized by TLR-mediated T cell dysregulation, including autoimmune diseases.

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