LIGHT is critical for IL-12 production by dendritic cells, optimal CD4 + Th1 cell response, and resistance to Leishmania major

Guilian Xu, Dong Liu, Ifeoma Okwor, Yang Wang, Heinrich Korner, Sam K.P. Kung, Yang Xin Fu, Jude E. Uzonna

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)6901-6909
Number of pages9
JournalJournal of Immunology
Volume179
Issue number10
DOIs
StatePublished - Nov 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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