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  • Title: TRANCE-RANK costimulation is required for IL-12 production and the initiation of a Th1-type response to Leishmania major infection in CD40L-deficient mice.
    Author: Padigel UM, Kim N, Choi Y, Farrell JP.
    Journal: J Immunol; 2003 Nov 15; 171(10):5437-41. PubMed ID: 14607948.
    Abstract:
    Blockade of TNF-related activation-induced cytokine (TRANCE)-receptor activator of NF-kappaB (RANK) interaction reverses healing in CD40L(-/-) mice infected with Leishmania major. Although previous studies demonstrated a requirement for CD40-CD40L interaction in production of IL-12 and the development of resistance to Leishmania infection, we recently showed that CD40L(-/-) mice control infection when inoculated with low numbers of parasites and that cells from these mice produce IL-12. Here, we show that in vivo treatment with a TRANCE receptor fusion protein results in a decrease in numbers of IL-12 producing cells as well as a shift from a dominant Th1 to Th2 type response in infected mice. These results demonstrate that CD40L(-/-) mice use the TRANCE-RANK costimulatory pathway to promote IL-12 production and the activation of a protective Th1 type response.
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