@article{26987,
  author = {Shah JA and Berrington WR and Vary J and Wells R and Peterson GJ and Kunwar CB and Khadge S and Hagge D and Hawn TR},
  title = {Genetic Variation in TOLLIP is Associated with Leprosy Susceptibility and Cutaneous IL-1 Receptor Antagonist Expression.},
  abstract = {<p>Editor's Abstract: Leprosy is a chronic disease characterized by skin and peripheral nerve pathology and immune responses that fail to control Mycobacterium leprae. Toll-Interacting Protein (TOLLIP) regulates TLR and IL-1R signaling against mycobacteria. We analyzed mRNA expression of candidate immune genes in 85 leprosy skin biopsies. TOLLIP mRNA was highly and specifically correlated with IL-1 receptor antagonist (IL-1Ra). In a case-control gene association study with 477 cases and 1021 controls in Nepal, TOLLIP SNP rs3793964 TT genotype was associated with increased susceptibility to leprosy (recessive, p=1.4 x 10(-3)) and with increased skin expression of TOLLIP and IL-1Ra. Stimulation of TOLLIP-deficient monocytes with M. leprae produced significantly less IL-1Ra (p&lt;0.001) compared to control. These data suggest that M. leprae upregulates IL-1Ra by a TOLLIP-dependent mechanism. Inhibition of TOLLIP may decrease an individual's susceptibility to leprosy and offer a novel therapeutic target for IL-1-dependent diseases.</p>
},
  year = {2015},
  journal = {The Journal of infectious diseases},
  publisher = {Oxford Journals },
  issn = {1537-6613},
  doi = {10.1093/infdis/jiv570},
  language = {eng},
}