Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
Authors Saini C, Kumar P, Tarique M, Sharma A, Ramesh V
Received 2 May 2018
Accepted for publication 17 July 2018
Published 28 September 2018 Volume 2018:11 Pages 377—388
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 4
Editor who approved publication: Dr Ning Quan
Chaman Saini,1 Praveen Kumar,1,2 Mohd Tarique,1 Alpana Sharma,1 Venkatesh Ramesh3
1Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India; 2Department of Microbiology, Government Medical College, Kota, India; 3Department of Dermatology, Safdarjung Hospital, New Delhi, India
Background: The clinical forms of cutaneous tuberculosis (CTB) consist of a spectrum that reflects the host’s immune response to Mycobacterium tuberculosis; it provides an ideal model to study the immunological dysregulation in humans. IL-17 plays an important role in initial immune response and is involved in both immune-mediated protection and pathology during M. tuberculosis infection. TGF-β producing regulatory T-cells (Tregs) are high in leprosy patients and responsible for immune suppression. However, in CTB, the involvement of Tregs and Th17 remains unevaluated.
Objective: To study the role of proinflammatory Th17 and Treg cells in the human CTB.
Methods: Blood and skin biopsies of CTB patients and healthy controls (HC) were included in the study. Flow cytometric analysis of IL-17, FOXP3, and TGF-β in blood was done followed by immunohistochemistry on paraffin-embedded skin sections. Expression of IFN-γ, TGF-β, and IL-17 was evaluated by quantitative real-time PCR.
Results: We found significant (P<0.0002) lower expression of proinflammatory IL-17 and IFN-γ (P<0.01) in CTB skins as compared to HC. However, the frequency of TGF-β producing Treg cells was found to be high in CTB patients (P<0.001) as compared to HC. A similar type of profile was observed by flow cytometric analysis. Treg cells produced suppressive cytokine TGF-β which showed a positive correlation with FOXP3 gene expression.
Conclusion: Our study found an increase in lineage-specific CD4+ Tregs in CTB as compared to the HC individuals. Such cells secrete TGF-β, a suppressive cytokine and may play a role in negatively regulating the T-cell immune responses in CTB. In addition, Tregs with TGF-β may downregulate Th17 cell responses leading to the antigen-specific anergy associated with CTB patients.
Keywords: FOXP3, IFN-γ, TGF-β, IL-17, regulatory T cells, cutaneous tuberculosis
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