02014nas a2200289   4500000000100000008004100001653001200042653001100054653001200065653001200077653001100089653001000100653000800110653002000118653002400138653002900162653002800191100001000219700001500229700001600244700001200260700002700272700001200299245011400311520128500425022001401710       2019                            d10aleprosy10aDelta110aJagged110aJagged210aNotch110aPGL-110aWCS10aNotch signaling10alymphoproliferation10aT helper cell activation10aTh1/Th2 differentiation1 aDua B1 aUpadhyay R1 aNatarajan M1 aArora M1 aNarayanaswamy Balaji K1 aJoshi B00aNotch signaling induces lymphoproliferation, T helper cell activation and Th1/Th2 differentiation in leprosy.3 a<p>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 Notch1 signaling pathway. Higher percentage of Notch1expressing 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 Jagged1 on Th cells. Interestingly activation of Notch1 signaling pathway induced lymphoproliferation in BL/LL cases in response of PGL-1. Activation of Notch1 signaling was also found to induce the expression of T cell activation markers CD25, CD69 and Th1 cytokine IFN-γ in response to M. leprae antigens. Immunomodulation through Notch1 signaling seen in our study could be helpful in augmenting Th1 response in leprosy.</p>
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