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

Bhavyata Dua1, Rajni Upadhyay1, Mohan Natrajan1

  • 1National JALMA Institute for Leprosy and Other Mycobacterial Diseases (ICMR), Agra, 282004, India.

Immunology Letters
|January 11, 2019
PubMed

Insights

This study reveals Notch1 signaling enhances T cell responses in leprosy by boosting T helper cell proliferation and IFN-γ production. Modulating Notch1 could improve T helper 1 immunity in leprosy patients.

Area of Science:

  • Immunology
  • Cellular Biology
  • Infectious Diseases

Background:

  • Leprosy pathogenesis involves complex T cell immune responses.
  • The role of Notch1 signaling in T cell immunity during leprosy remains underexplored.

Purpose of the Study:

  • To investigate the function of Notch1 signaling in regulating T cell immunity in leprosy.
  • To analyze the impact of Notch1 activation and inhibition on T cell responses in leprosy patients.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) from leprosy patients and healthy controls were stimulated with Mycobacterium leprae antigens.
  • Notch1 signaling pathway activation and inhibition were performed.
  • Lymphoproliferation was assessed using the lymphocyte transformation test.
  • Flow cytometry was used to analyze Notch1, its ligands (DLL1, Jagged1, Jagged2), T cell activation markers (CD25, CD69), and Th1-Th2 cytokines (IFN-γ).

Main Results:

  • Higher Notch1 expression on T helper cells was observed in TT/BT leprosy cases.
  • DLL1 expression on T helper cells was elevated in TT/BT and BL/LL cases.
  • Mycobacterium leprae antigens induced Jagged1 expression on T helper cells.
  • Notch1 pathway activation promoted lymphoproliferation in BL/LL cases and increased T cell activation markers and IFN-γ production in response to M. leprae antigens.

Conclusions:

  • Notch1 signaling plays a significant role in modulating T cell immunity in leprosy.
  • Activation of Notch1 signaling can enhance T helper 1 immune responses, suggesting its potential as an immunomodulatory target in leprosy treatment.

Keywords:
Delta1Jagged1Jagged2LeprosyNotch1PGL-1WCS

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