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-ß 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-ß in blood was done followed by immunohistochemistry on paraffin-embedded skin sections. Expression of IFN-γ, TGF-ß, 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-ß 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-ß 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-ß, a suppressive cytokine and may play a role in negatively regulating the T-cell immune responses in CTB. In addition, Tregs with TGF-ß may downregulate Th17 cell responses leading to the antigen-specific anergy associated with CTB patients.