02723nas a2200529   4500000000100000008004100001260001300042653001600055653003500071653001500106653001000121653003100131653001700162653001700179653001100196653003500207653001100242653002900253653001800282653004100300653001800341653001200359653003000371653000900401653001600410653003200426653002000458653001400478653001300492653001800505653003000523653003600553653001900589653001600608100001200624700001300636700001000649700001100659700001300670700001200683245010000695300001100795490000700806050001700813520134900830022001402179       2013                            d  c2013 Dec10aAcetylation10aActive Transport, Cell Nucleus10aAdolescent10aAdult10aCD4-Positive T-Lymphocytes10aCell Nucleus10aCyclosporine10aFemale10aForkhead Transcription Factors10aHumans10aImmunosuppressive Agents10aInterleukin-210aInterleukin-2 Receptor alpha Subunit10aIsoquinolines10aleprosy10aLeukocyte Common Antigens10aMale10aMiddle Aged10aNFATC Transcription Factors10aPhosphorylation10aPyridines10aPyrroles10aSmad3 Protein10aT-Lymphocytes, Regulatory10aTransforming Growth Factor beta10aUbiquitination10aYoung Adult1 aKumar S1 aNaqvi RA1 aAli R1 aRani R1 aKhanna N1 aRao D N00aCD4+CD25+ T regs with acetylated FoxP3 are associated with immune suppression in human leprosy.  a513-200 v56  aKUMAR 2013 d3 a<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>  a1872-9142