Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), New Delhi 110029, India.
Mol Immunol. 2013 Dec;56(4):513-20. doi: 10.1016/j.molimm.2013.04.015. Epub 2013 Aug 1.
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.
麻风病是一种由麻风分枝杆菌感染引起的慢性人类疾病。调节性 T 细胞（Treg）在各种疾病中具有重要意义已得到证实。然而，在麻风病中，Treg 是否能在疾病进展过程中介导免疫抑制作用仍不清楚。在本研究中，我们提出了导致 Treg 细胞高比例的假设机制，并研究了其在人类麻风病中的意义。高水平的 TGF-β，随后是 FoxP3(+)幼稚和记忆（CD4(+)CD45RA(+)/RO(+））T 细胞的适应性，是导致疾病进展过程中 Treg 细胞大量产生的主要潜在因素。此外，发现 TGF-β与 SMAD3 和 NFAT 的磷酸化介导的核内输入有关，这些因子向 BL/LL 极移动，以促进这些细胞中 FoxP3 的表达，这与在 TGF-β和 IL-2 存在的情况下，在 CD4(+)CD25(+)细胞中使用 SMAD3（SIS3）和 NFAT（环孢菌素 A）的核抑制剂后得到的结果一致。有趣的是，BL/LL 患者 Treg 细胞中 FoxP3 的低泛素化被揭示为赋予 FoxP3 稳定性的主要驱动力，而 FoxP3 又与 Treg 的抑制潜力有关。本研究还指出了麻风病中存在 CD4(+)CD25(+)IL-10(+)Treg 亚群（Tr1）。
