Increased IL-35 producing Tregs and CD19+IL-35+ cells are associated with disease progression in leprosy patients. (March 2017)

• Record Type: Journal Article
• Authors: Tarique, Mohd; Saini, Chaman; Naqvi, Raza Ali; Khanna, Neena; Rao, D.N.
• Is Part Of: Cytokine. Volume 91(2017)
• Page Start: 82
• Page End: 88
• Publication Date: 2017-03
• Subjects: Leprosy -- IL-35 -- PD-1 -- Treg -- Breg; Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2016.12.011
• Languages: English
• ISSNs: 1043-4666

Abstract

Highlights: IL-35 producing Treg increases from BT to BL/LL pole of leprosy. CD19 + IL-35 + cell increases from BT to BL/LL pole of leprosy. IL-35 plays important role in the progression of the disease. IL-35 shows positive correlation with Bacteriological index (BI). 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 48 h. 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.