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

ABSTRACT:

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-? 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-? in blood was done followed by immunohistochemistry on paraffin-embedded skin sections. Expression of IFN-?, TGF-?, 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-? (P<0.01) in CTB skins as compared to HC. However, the frequency of TGF-? 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-? 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-?, a suppressive cytokine and may play a role in negatively regulating the T-cell immune responses in CTB. In addition, Tregs with TGF-? may downregulate Th17 cell responses leading to the antigen-specific anergy associated with CTB patients.

SUBMITTER: Saini C 

PROVIDER: S-EPMC6168067 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature