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LIGHT is critical for IL-12 production by dendritic cells, optimal CD4(+) th1 cell response, and resistance to leishmania major
journal contributionposted on 2023-05-17, 07:47 authored by Xu, G, Liu, D, Okwor, I, Wang, Y, Heinrich KornerHeinrich Korner, Kung, SKP, Fu, YX, Uzonna, JE
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-Î³ and LPS stimulation in vitro. Furthermore, blockade of LIGHT in vitro and in vivo with HVEM-Ig and LT Î² receptor (LTÎ²R)-Ig leads to impaired IL-12 production and defective polyclonal and Ag-specific IFN-Î³ production in vivo. In an infection model, injection of HVEM-Ig or LTÎ²R-Ig into the usually resistant C57BL/6 mice results in defective IL-12 and IFN-Î³ 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 LTÎ²R-Ig was also reproduced in LIGHT-/- â†’ RAG1-/- chimeric mice. In contrast, L. major-infected LTÎ²-/- mice do not develop acute disease, suggesting that the effect of LTÎ²R-Ig is not due to blockade of membrane LT (LTÎ±1Î²2) signaling. Collectively, our data show that LIGHT plays a critical role for optimal IL-12 production by DC and the development of IFN-Î³-producing CD4+ Th1 cells and its blockade results in severe susceptibility to Leishmania major. Copyright Â© 2007 by The American Association of Immunologists, Inc.
Publication titleJournal of Immunology
Department/SchoolMenzies Institute for Medical Research
PublisherAmer Assoc Immunologists
Place of publication9650 Rockville Pike, Bethesda, USA, Md, 20814