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

Sudhir Kumar, Raza Ali Naqvi, Riyasat Ali, Richa Rani, Neena Khanna, D. N. Rao

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)431-439
Number of pages9
JournalEuropean Journal of Immunology
Volume44
Issue number2
DOIs
StatePublished - Feb 1 2014
Externally publishedYes

Fingerprint

Lepromatous Leprosy
Leprosy
Borderline Leprosy
Multibacillary Leprosy
T-Lymphocytes
Tuberculoid Leprosy
Paucibacillary Leprosy
Mycobacterium leprae
Histone Deacetylases
Propidium
Annexin A5
Regulatory T-Lymphocytes
Transferases
Genetic Promoter Regions
Histones
Genes
Communicable Diseases
Chronic Disease
Down-Regulation
Staining and Labeling

Keywords

  • Competitive fitness
  • FoxP3
  • HDAC7
  • HDAC9
  • Histone acetyl transferase
  • Leprosy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

FoxP3 provides competitive fitness to CD4+CD25+ T cells in leprosy patients via transcriptional regulation. / Kumar, Sudhir; Naqvi, Raza Ali; Ali, Riyasat; Rani, Richa; Khanna, Neena; Rao, D. N.

In: European Journal of Immunology, Vol. 44, No. 2, 01.02.2014, p. 431-439.

Research output: Contribution to journalArticle

Kumar, Sudhir ; Naqvi, Raza Ali ; Ali, Riyasat ; Rani, Richa ; Khanna, Neena ; Rao, D. N. / FoxP3 provides competitive fitness to CD4+CD25+ T cells in leprosy patients via transcriptional regulation. In: European Journal of Immunology. 2014 ; Vol. 44, No. 2. pp. 431-439.
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