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.
BT - European journal of immunology C1 - http://www.ncbi.nlm.nih.gov/pubmed/24214631?dopt=Abstract DA - 2014 Feb DO - 10.1002/eji.201343649 IS - 2 J2 - Eur. J. Immunol. LA - eng N2 -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.
PY - 2014 SP - 431 EP - 9 T2 - European journal of immunology TI - FoxP3 provides competitive fitness to CD4⁺CD25⁺ T cells in leprosy patients via transcriptional regulation. VL - 44 SN - 1521-4141 ER -