@article{24892,
  keywords = {Adolescent, Adult, CD4-Positive T-Lymphocytes, Cell Proliferation, Cell Survival, CTLA-4 Antigen, Female, Forkhead Transcription Factors, Gene Expression Regulation, Histone Deacetylases, Humans, Interleukin-2, Interleukin-2 Receptor alpha Subunit, leprosy, Male, MicroRNAs, Middle Aged, Mycobacterium leprae, Promoter Regions, Genetic, T-Lymphocytes, Regulatory, Th1 Cells, Th2 Cells, Transcription, Genetic, Young Adult},
  author = {Kumar S and Naqvi RA and Ali R and Rani R and Khanna N and Rao D N},
  title = {FoxP3 provides competitive fitness to CD4⁺CD25⁺ T cells in leprosy patients via transcriptional regulation.},
  abstract = {<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>},
  year = {2014},
  journal = {European journal of immunology},
  volume = {44},
  pages = {431-9},
  month = {2014 Feb},
  issn = {1521-4141},
  doi = {10.1002/eji.201343649},
  language = {eng},
}