02727nas a2200481   4500000000100000008004100001260001300042653001500055653001000070653003100080653002300111653001800134653001900152653001100171653003500182653003100217653002500248653001100273653001800284653004100302653001200343653000900355653001400364653001600378653002500394653003000419653003000449653001400479653001400493653002700507653001600534100001200550700001300562700001000575700001100585700001300596700001200609245011600621300001000737490000700747520147700754022001402231       2014                            d  c2014 Feb10aAdolescent10aAdult10aCD4-Positive T-Lymphocytes10aCell Proliferation10aCell Survival10aCTLA-4 Antigen10aFemale10aForkhead Transcription Factors10aGene Expression Regulation10aHistone Deacetylases10aHumans10aInterleukin-210aInterleukin-2 Receptor alpha Subunit10aleprosy10aMale10aMicroRNAs10aMiddle Aged10aMycobacterium leprae10aPromoter Regions, Genetic10aT-Lymphocytes, Regulatory10aTh1 Cells10aTh2 Cells10aTranscription, Genetic10aYoung Adult1 aKumar S1 aNaqvi RA1 aAli R1 aRani R1 aKhanna N1 aRao D N00aFoxP3 provides competitive fitness to CD4⁺CD25⁺ T cells in leprosy patients via transcriptional regulation.  a431-90 v443 a<p>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 7/9 in the nucleus of CD4⁺CD25⁺ T cells derived from borderline lepromatous leprosy/lepromatous leprosy (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 histone acetyl transferases. 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 & propidium iodide 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 borderline tuberculoid leprosy/tuberculoid leprosy and healthy controls. Taken together, the study shows the orchestration of FoxP3 leading to competitive fitness of Treg cells in leprosy.</p>  a1521-4141