Th3 Immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b

Sudhir Kumar, Raza A. Naqvi, Neena Khanna, Pankaj Pathak, D. N. Rao

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)133-142
Number of pages10
JournalClinical Immunology
Volume141
Issue number2
DOIs
StatePublished - Nov 2011

Bibliographical note

Funding Information:
The authors are thankful to ICMR and CSIR for providing financial support to carry out this work. We are also thankful to Mr. Pankaj Pathak, Department of Pathology, AIIMS, for real time PCR analysis in this study.

Keywords

  • Leprosy
  • MLCwA
  • Mycobacterium leprae
  • TGF-β
  • Th3

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