Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis

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,...

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Autores principales:	Saini C, Kumar P, Tarique M, Sharma A, Ramesh V
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	FOXP3 IFN-γ TGF-β and IL-17 Regulatory T cells Cutaneous tuberculosis Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/bd246579ed234d20839cfbb251999290
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spelling	oai:doaj.org-article:bd246579ed234d20839cfbb2519992902021-12-02T11:12:50ZRegulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis1178-7031https://doaj.org/article/bd246579ed234d20839cfbb2519992902018-09-01T00:00:00Zhttps://www.dovepress.com/regulatory-t-cells-antagonize-proinflammatory-response-of-il-17-during-peer-reviewed-article-JIRhttps://doaj.org/toc/1178-7031Chaman 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 tuberculosisSaini CKumar PTarique MSharma ARamesh VDove Medical PressarticleFOXP3IFN-γTGF-β and IL-17Regulatory T cellsCutaneous tuberculosisPathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 11, Pp 377-388 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	FOXP3 IFN-γ TGF-β and IL-17 Regulatory T cells Cutaneous tuberculosis Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	FOXP3 IFN-γ TGF-β and IL-17 Regulatory T cells Cutaneous tuberculosis Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Saini C Kumar P Tarique M Sharma A Ramesh V Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
description	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
format	article
author	Saini C Kumar P Tarique M Sharma A Ramesh V
author_facet	Saini C Kumar P Tarique M Sharma A Ramesh V
author_sort	Saini C
title	Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
title_short	Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
title_full	Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
title_fullStr	Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
title_full_unstemmed	Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis
title_sort	regulatory t cells antagonize proinflammatory response of il-17 during cutaneous tuberculosis
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/bd246579ed234d20839cfbb251999290
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Regulatory T cells antagonize proinflammatory response of IL-17 during cutaneous tuberculosis

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