FoxP3 provides competitive fitness to CD4(+) CD25(+) T cells in leprosy patients via transcriptional regulation.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. FoxP3 have been shown to have important implications in various diseases. The present study describes the mechanism of action of FoxP3 in CD4(+) CD25(+) T cells derived from leprosy patients. Increased molecular interactions of FoxP3 with Histone deacetylases (HDAC7/9) in the nucleus of CD4(+) CD25(+) T cells derived from lepromatous leprosy patients (BL/LL) patients were found to be responsible for FoxP3-driven immune suppression activities during the progression of leprosy. Further, downregulation of CTLA-4 and CD25 genes in siFoxP3-treated PBMCs derived from BL/LL patients elucidated the transcription-activating nature of FoxP3. This observation was supported by direct binding of FoxP3 to the promoter region of the CTLA-4 and CD25 genes, and FoxP3's molecular interaction with HATs. The study also revealed that the increased expression of miR155 in CD4(+) CD25(+) cells from BL/LL governs the competitive fitness of these cells. Again, reduced Annexin V&PI staining and Nur77 expression, and concomitantly increased Ki-67 positivity suggested that CD4(+) CD25(+) cells derived from BL/LL patients are more competitively fit than those from BT/TT and healthy controls. Taken together, the study shows the orchestration of FoxP3 leading to competitive fitness of Treg cells in leprosy. This article is protected by copyright. All rights reserved.