IL-12 and IL-23 modulate plasticity of FoxP3+ regulatory T cells in human Leprosy

Mohd Tarique, Chaman Saini, Raza Ali Naqvi, Neena Khanna, Alpana Sharma, D. N. Rao

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host's immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host by producing IL-10 and TGF-β cytokines. In leprosy, plasticity of Tregs remain unstudied. This is the first study describing the conversion of Tregs into Th1-like and Th17-like cells using in vitro cytokine therapy in leprosy patients. Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA), rIL-12 and rIL-23 for 48 h. Expression of FoxP3 in CD4+CD25+ Tregs, intracellular cytokines IFN-γ, TGF-β, IL-10 and IL-17 in Tregs cells were evaluated by flow cytometry (FACS) after stimulation. rIL-12 treatment increases the levels of pStat4 in Tregs and IFN-γ production. In the presence of rIL-23, pStat3+ and IL-17A+ cells increase. rIL-12 and r—IL-23 treatment downregulated the FoxP3 expression, IL-10 and TGF-β production by Tregs and enhances the expression of co-stimulatory molecules (CD80, CD86). In conclusion rIL-12 converts Tregs into IFN-γ producing cells through STAT-4 signaling while rIL-23 converts Tregs into IL-17 producing cells through STAT-3 signaling in leprosy patients. This study may helpful to provide a new avenue to overcome the immunosuprression in leprosy patients using in vitro cytokine.

Original languageEnglish (US)
Pages (from-to)72-81
Number of pages10
JournalMolecular Immunology
Volume83
DOIs
StatePublished - Mar 1 2017

Keywords

  • Leprosy
  • Th1-like
  • Tregs
  • rIL-12
  • rIL-23

Fingerprint Dive into the research topics of 'IL-12 and IL-23 modulate plasticity of FoxP3<sup>+</sup> regulatory T cells in human Leprosy'. Together they form a unique fingerprint.

Cite this