Mohd Tarique1, Chaman Saini1, Raza Ali Naqvi1, Neena Khanna2, D N Rao3. 1. Department of Biochemistry, All India Institute of Medical Sciences, AIIMS, New Delhi 110029, India. 2. Department of Dermatovenerology, All India Institute of Medical Sciences, AIIMS, New Delhi 110029, India. 3. 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.
Abstract
BACKGROUND: 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. OBJECTIVE: To study the role of IL-35 producing Tregs and Bregs in the human leprosy. METHODS: 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. RESULTS: 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. CONCLUSION: 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. Copyright Â
BACKGROUND: 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 leprosypatients and responsible for immune suppression and M. leprae specific T cells anergy. In leprosy, involvement of IL-35 producing Tregs and Bregs remain unstudied. OBJECTIVE: To study the role of IL-35 producing Tregs and Bregs in the humanleprosy. METHODS: Peripheral blood mononuclear cells from leprosypatients 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. RESULTS: The frequency of IL-35 producing Tregs and Bregs cells were found to be high in leprosypatients (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 leprosypatients. CONCLUSION: 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 leprosypatients with a new paradigm (IL-35 producing Tregs and Bregs) that is beyond TGF-β and IL-10 producing Treg cells. Copyright Â
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Authors: Mohd Tarique; Huma Naz; Santosh V Kurra; Chaman Saini; Raza Ali Naqvi; Reeta Rai; Mohd Suhail; Neena Khanna; Donthamshetty N Rao; Alpana Sharma Journal: Front Immunol Date: 2018-07-23 Impact factor: 7.561
Authors: Mohammad Tarique; Huma Naz; Chaman Saini; Mohd Suhail; Hari Shankar; Neena Khanna; Alpana Sharma Journal: Front Immunol Date: 2020-08-06 Impact factor: 7.561