LACC1 Regulates TNF and IL-17 in Mouse Models of Arthritis and Inflammation

J Immunol. 2019 Jan 1;202(1):183-193. doi: 10.4049/jimmunol.1800636. Epub 2018 Dec 3.


Both common and rare genetic variants of laccase domain-containing 1 (LACC1, previously C13orf31) are associated with inflammatory bowel disease, leprosy, Behcet disease, and systemic juvenile idiopathic arthritis. However, the functional relevance of these variants is unclear. In this study, we use LACC1-deficient mice to gain insight into the role of LACC1 in regulating inflammation. Following oral administration of Citrobacter rodentium, LACC1 knockout (KO) mice had more severe colon lesions compared with wildtype (WT) controls. Immunization with collagen II, a collagen-induced arthritis (CIA) model, resulted in an accelerated onset of arthritis and significantly worse arthritis and inflammation in LACC1 KO mice. Similar results were obtained in a mannan-induced arthritis model. Serum and local TNF in CIA paws and C. rodentium colons were significantly increased in LACC1 KO mice compared with WT controls. The percentage of IL-17A-producing CD4+ T cells was elevated in LACC1 KO mice undergoing CIA as well as aged mice compared with WT controls. Neutralization of IL-17, but not TNF, prevented enhanced mannan-induced arthritis in LACC1 KO mice. These data provide new mechanistic insight into the function of LACC1 in regulating TNF and IL-17 during inflammatory responses. We hypothesize that these effects contribute to immune-driven pathologies observed in individuals carrying LACC1 variants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / microbiology
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology*
  • Citrobacter rodentium / physiology*
  • Disease Models, Animal
  • Enterobacteriaceae Infections / immunology*
  • Genetic Predisposition to Disease
  • Humans
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Interleukin-17 / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Polymorphism, Genetic
  • Th17 Cells / immunology*
  • Tumor Necrosis Factors / metabolism


  • Interleukin-17
  • Intracellular Signaling Peptides and Proteins
  • Lacc1 protein, mouse
  • Tumor Necrosis Factors
  • Oxidoreductases

Supplementary concepts

  • Rheumatoid Arthritis, Systemic Juvenile