Notch signaling induces lymphoproliferation, T helper cell activation and Th1/Th2 differentiation in leprosy

摘要

The present study evaluates role of Notch1 signaling in the regulation of T cell immunity in leprosy. Peripheral blood mononuclear cells from leprosy patients and healthy controls were activated with Mycobacterium leprae antigens along with activation of Notch1 signaling pathway and then lymphoproliferation was analyzed by lymphocytes transformation test and the expression of Notch1 and its ligands DLL1, Jagged1 and Jagged 2, T cell activation marker and Th1-Th2 cytokines on Th cells in PBMCs of study subjects were analyzed by flow cytometry. Further, these parameters were also analyzed after inhibition of Notchl signaling pathway. Higher percentage of Notchlexpressing Th cells were noted in TT/BT cases and higher percentage of DLL1 expressing Th cells in TT/BT and BL/LL cases. M. leprae antigens were found to induce the expression of Jaggedl on Th cells. Interestingly activation of Notchl signaling pathway induced lymphoproliferation in BL/LL cases in response of PGL-1. Activation of Notchl signaling was also found to induce the expression of T cell activation markers CD25, CD69 and Thl cytokine IFN-gamma in response to M. leprae antigens. Immunomodulation through Notchl signaling seen in our study could be helpful in augmenting Thl response in leprosy.