@article{24338,
  keywords = {Acetylation, Active Transport, Cell Nucleus, Adolescent, Adult, CD4-Positive T-Lymphocytes, Cell Nucleus, Cyclosporine, Female, Forkhead Transcription Factors, Humans, Immunosuppressive Agents, Interleukin-2, Interleukin-2 Receptor alpha Subunit, Isoquinolines, leprosy, Leukocyte Common Antigens, Male, Middle Aged, NFATC Transcription Factors, Phosphorylation, Pyridines, Pyrroles, Smad3 Protein, T-Lymphocytes, Regulatory, Transforming Growth Factor beta, Ubiquitination, Young Adult},
  author = {Kumar S and Naqvi RA and Ali R and Rani R and Khanna N and Rao D N},
  title = {CD4+CD25+ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy.},
  abstract = {<p>Leprosy is a chronic human disease that results from infection of Mycobacterium leprae. T reg cells have been shown to have important implications in various diseases. However, in leprosy, it is still unclear whether T regs can mediate immune suppression during progression of the disease. In the present study, we have proposed the putative mechanism leading to high proportion of T reg cells and investigated its significance in human leprosy. High levels of TGF-β followed by adaptation of FoxP3(+) naive and memory (CD4(+)CD45RA(+)/RO(+)) T cells were observed as the principal underlying factors leading to higher generation of T reg cells during disease progression. Furthermore, TGF-β was found to be associated with increased phosphorylation-mediated-nuclear-import of SMAD3 and NFAT towards BL/LL pole to facilitate FoxP3 expression in these cells, the same as justified after using nuclear inhibitors of SMAD3 (SIS3) and NFAT (cyclosporin A) in CD4(+)CD25(+) cells in the presence of TGF-β and IL-2. Interestingly, low ubiquitination of FoxP3 in T reg cells of BL/LL patients was revealed to be a major driving force in conferring stability to FoxP3 which in turn is linked to suppressive potential of T regs. The present study has also pinpointed the presence of CD4(+)CD25(+)IL-10(+) sub class of T regs (Tr1) in leprosy. </p>},
  year = {2013},
  journal = {Molecular immunology},
  volume = {56},
  pages = {513-20},
  month = {2013 Dec},
  issn = {1872-9142},
  doi = {10.1016/j.molimm.2013.04.015},
  language = {eng},
}