title: IL-12 and IL-23 modulate plasticity of FoxP3+regulatory T cells in human Leprosy.
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 48h. 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.
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Tarique
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India.
authors.forename: Chaman
authors.initials: C
authors.lastname: Saini
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India.
authors.forename: Raza Ali
authors.initials: RA
authors.lastname: Naqvi
authors.affiliation: Department of Dermatovenerology, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India.
authors.forename: Neena
authors.initials: N
authors.lastname: Khanna
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India. Electronic address: dralpanasharma@gmail.com.
authors.forename: Alpana
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi, 110029, India; GITAM Institute of Medical Sciences and Research, GITAM University, Rushikonda, Visakhapatnam, 530045, India. Electronic address: dnrao31151@gmail.com.
authors.forename: D N
authors.initials: DN
authors.lastname: Rao
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D053759:Interleukin-23 / Q000276:immunology*; D007918:Leprosy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053759:Interleukin-23; D018664:Interleukin-12
keywords: Leprosy; Th1-like; Tregs; rIL-12; rIL-23