Th3 Immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b
Clinical Immunology, ISSN: 1521-6616, Vol: 141, Issue: 2, Page: 133-142
2011
- 41Citations
- 36Captures
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Metrics Details
- Citations41
- Citation Indexes41
- 41
- CrossRef30
- Captures36
- Readers36
- 36
Article Description
Leprosy is a chronic human disease; primarily affecting skin, peripheral nerves, eyes, testis etc. Comprehensive-expressional-profiling of Th1–Th2–Th3 associated markers (84 genes) using qRT-PCR array, negated the previously prevailing notion, Th2 bias towards multibacillary stage of leprosy. High production TGF-β further supported the dearth of any immune response(s) in leprosy progression. Over expression of Cbl-b, could emerge as plausible reason for contributing T cell hyporesponsiveness, possibly by degradation of T cells signaling molecules. Anti-TGF-β treatments further confirm the TGF-β-dependent-Cbl-b overexpression in multibacillary patients. Diminished Cbl-b expression in CTLA-4 knockout studies using siRNA, provided other evidence towards T cell hyporesponsiveness. Further, high T cell proliferation and IL-2 production in PBMC cultures treated with anti-TGF-β and siRNA offers here a strategy to revert T cell hyporesponsiveness by downregulating Cbl-b expression in leprosy. Thus, this study negates Th2 bias and substantiates molecular cross-talk amongst TGF-β-CTLA-4-Cbl-b eventually leads to M. leprae persistence.
Bibliographic Details
http://www.sciencedirect.com/science/article/pii/S1521661611001938; http://dx.doi.org/10.1016/j.clim.2011.06.007; http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80054831920&origin=inward; http://www.ncbi.nlm.nih.gov/pubmed/21807564; https://linkinghub.elsevier.com/retrieve/pii/S1521661611001938; https://dx.doi.org/10.1016/j.clim.2011.06.007
Elsevier BV
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