The immune modulatory mechanisms of lanthionine synthetase C-like 2

Philipson, C., C. Hetzel, K. Eden, R. Hontecillas and J. Bassaganya-Riera (2015) The immune modulatory mechanisms of lanthionine synthetase C-like 2, American Association of Immunologists Annual Meeting, New Orleans, LA

Lanthionine synthetase C-like protein 2 (LANCL2) has emerged as a novel therapeutic target for metabolic, infectious and immune-mediated diseases. We previously demonstrated that directly targeting LANCL2 through treatment with abscisic acid or 61610 results in efficacious anti-inflammatory responses during DSS-induced colitis however molecular mechanisms underlying this immunomodulatory function remain elusive. Here we report for the first time the use of LANCL2-deficient mice to investigate the mechanism of action and cell specificity of the protein. At the cellular level, bone marrow derived macrophages (BMDM), RAW cells, and gastric epithelial cells express comparable levels of basal LANCL2 mRNA. LPS-mediated inflammation in BMDM increased both mRNA and protein levels of LANCL2 that peaked 6 hours post-challenge and subsequently returned to normal levels after 12 hours. Similarly, DSS-induced colitis induced expression of LANCL2 in the colons of wild-type (WT) mice and correlated with elevated levels of proinflammatory cytokines. Interestingly, the absence of LANCL2 did not cause significant alterations in infiltrating cellular phenotypes however LANCL2 deficiency permitted exaggerated IL17 and IFNγ expression in colonic tissue when compared to WT counterparts at day 7 post-challenge. In conclusion, our findings indicate that LANCL2 is a novel regulator of inflammation that functions predominantly at the molecular level to down-regulate excessive inflammatory responses.