TY - JOUR KW - Acetylation KW - Active Transport, Cell Nucleus KW - Adolescent KW - Adult KW - CD4-Positive T-Lymphocytes KW - Cell Nucleus KW - Cyclosporine KW - Female KW - Forkhead Transcription Factors KW - Humans KW - Immunosuppressive Agents KW - Interleukin-2 KW - Interleukin-2 Receptor alpha Subunit KW - Isoquinolines KW - leprosy KW - Leukocyte Common Antigens KW - Male KW - Middle Aged KW - NFATC Transcription Factors KW - Phosphorylation KW - Pyridines KW - Pyrroles KW - Smad3 Protein KW - T-Lymphocytes, Regulatory KW - Transforming Growth Factor beta KW - Ubiquitination KW - Young Adult AU - Kumar S AU - Naqvi RA AU - Ali R AU - Rani R AU - Khanna N AU - Rao D N AB -

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.

BT - Molecular immunology C1 - http://www.ncbi.nlm.nih.gov/pubmed/23911408?dopt=Abstract CN - KUMAR 2013 d DA - 2013 Dec DO - 10.1016/j.molimm.2013.04.015 IS - 4 J2 - Mol. Immunol. LA - eng N2 -

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.

PY - 2013 SP - 513 EP - 20 T2 - Molecular immunology TI - CD4+CD25+ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy. VL - 56 SN - 1872-9142 ER -