LIGHT is critical for IL-12 production by dendritic cells, optimal CD4(+) th1 cell response, and resistance to leishmania major
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Xu, G and Liu, D and Okwor, I and Wang, Y and Korner, H and Kung, SKP and Fu, YX and Uzonna, JE, LIGHT is critical for IL-12 production by dendritic cells, optimal CD4(+) th1 cell response, and resistance to leishmania major, Journal of Immunology, 179, (10) pp. 6901-6909. ISSN 0022-1767 (2007) [Refereed Article]
Although studies indicate LIGHT (lymphotoxin (LT)-like, exhibits inducible expression and competes with HSV glycoprotein D for herpes virus entry mediator (HVEM), a receptor expressed by T lymphocytes) enhances inflammation and T cell-mediated immunity, the mechanisms involved in this process remain obscure. In this study, we assessed the role of LIGHT in IL-12 production and development of CD4+ Th cells type one (Th1) in vivo. Bone marrow-derived dendritic cells from LIGHT-/- mice were severely impaired in IL-12p40 production following IFN-γ and LPS stimulation in vitro. Furthermore, blockade of LIGHT in vitro and in vivo with HVEM-Ig and LT β receptor (LTβR)-Ig leads to impaired IL-12 production and defective polyclonal and Ag-specific IFN-γ production in vivo. In an infection model, injection of HVEM-Ig or LTβR-Ig into the usually resistant C57BL/6 mice results in defective IL-12 and IFN-γ production and severe susceptibility to Leishmania major that was reversed by rIL-12 treatment. This striking susceptibility to L. major in mice injected with HVEM-Ig or LTβR-Ig was also reproduced in LIGHT-/- → RAG1-/- chimeric mice. In contrast, L. major-infected LTβ-/- mice do not develop acute disease, suggesting that the effect of LTβR-Ig is not due to blockade of membrane LT (LTα1β2) signaling. Collectively, our data show that LIGHT plays a critical role for optimal IL-12 production by DC and the development of IFN-γ-producing CD4+ Th1 cells and its blockade results in severe susceptibility to Leishmania major. Copyright © 2007 by The American Association of Immunologists, Inc.
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