title: Increased IL-35 producing Tregs and CD19+IL-35+cells are associated with disease progression in leprosy patients.
abstract: The clinical forms of leprosy consist of a spectrum that reflects the host's immune response to the M. leprae; it provides an ideal model to study the host pathogen interaction and immunological dysregulation in humans. IL-10 and TGF-β producing Tregs are high in leprosy patients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied.
  
  
  
  To study the role of IL-35 producing Tregs and Bregs in the human leprosy.
  
  
  
  Peripheral blood mononuclear cells from leprosy patients were isolated and stimulated with M. leprae antigen (MLCwA) for 48h. Intracellular cytokine IL-35 was evaluated in CD4+CD25+Tregs, CD19+cells by FACS. Expression of PD-1 on CD4+CD25+Tregs, CD19+cells and its ligand (PD-L1) on B cells, CD11c cells were evaluated by flow cytometry (FACS). Serum IL-35 level was estimated by ELISA.
  
  
  
  The frequency of IL-35 producing Tregs and Bregs cells were found to be high in leprosy patients (p<0.0001) as compared to healthy controls. These cells produced suppressive cytokine IL-35 which showed positive correlation with bacteriological index (BI) and TGF-β producing Tregs, indicating its suppressive nature. We found higher expression of PD-1 on Tregs, B cell and its ligand (PD-L1) on antigen presenting cells in leprosy patients.
  
  
  
  This study point out a shift in our understanding of the immunological features that mediate and regulate the immune suppression and the disease progression in leprosy patients with a new paradigm (IL-35 producing Tregs and Bregs) that is beyond TGF-β and IL-10 producing Treg cells.
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; 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: D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood / Q000276:immunology*; D007918:Leprosy / Q000097:blood / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D000942:Antigens, Bacterial; D007378:Interleukins; C532417:interleukin-35, human
keywords: Breg; IL-35; Leprosy; PD-1; Treg