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.
Bibliographical noteFunding Information:
The authors are thankful to ICMR and CSIR for providing financial support to carry out this work. The authors would like to thank the staff of our laboratories in Department of Biochemistry, AIIMS, New Delhi, India , and to the individuals who agreed to take part in the study.
- Acetylated FoxP3
- M. leprae
- T regs