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

• Published in: Immunology letters 2019-03, Vol.207, p.6-16
• Main Authors: Dua, Bhavyata, Upadhyay, Rajni, Natrajan, Mohan, Arora, Mamta, Kithiganahalli Narayanaswamy, Balaji, Joshi, Beenu
• Format: Article
• Language: English
• Subjects: Antigens, Bacterial - immunology; Antigens, CD - metabolism; Antigens, Differentiation, T-Lymphocyte - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - metabolism; Cell Differentiation; Cell Proliferation; Cells, Cultured; Delta1; Disease Progression; Flow Cytometry; Glycolipids - immunology; Humans; Immunomodulation; Interferon-gamma - metabolism; Jagged-1 Protein - genetics; Jagged-1 Protein - metabolism; Jagged1; Jagged2; Lectins, C-Type - metabolism; Leprosy; Leprosy - immunology; Lymphocyte Activation; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mycobacterium leprae - immunology; Notch1; PGL-1; Receptor, Notch1 - metabolism; Signal Transduction; Th1 Cells - immunology; Th1-Th2 Balance; Th2 Cells - immunology; WCS
• ISSN: 0165-2478; 1879-0542
• DOI: 10.1016/j.imlet.2019.01.003

•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 and blocking of Notch1 signaling pathway and then lymphoproliferation, 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.•M. leprae antigens induced 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 and Th1 cytokine response to M. leprae antigens.•Immunomodulation through Notch1 signaling seen in our study could be helpful in augmenting Th1 response in leprosy. 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.