Self‐recognition through Dectin‐1 exacerbates liver inflammation

Abstract

AbstractDectin‐1 is a well‐characterized C‐type lectin receptor involved in anti‐fungal immunity through the recognition of polysaccharides; however, molecular mechanisms and outcomes initiated through self‐recognition have not been fully understood. Here, we purified a water‐soluble fraction from mouse liver that acts as a Dectin‐1 agonist. To address the physiological relevance of this recognition, we utilized sterile liver inflammation models. The CCl4‐induced hepatitis model showed that Dectin‐1 deficiency led to reduced inflammation through decreased inflammatory cell infiltration and lower pro‐inflammatory cytokine levels. Moreover, in a NASH model induced by streptozotocin and a high‐fat diet, hepatic inflammation and fibrosis were ameliorated in Dectin‐1‐deficient mice. The Dectin‐1 agonist activity was increased in the water‐soluble fraction from NASH mice, suggesting a potential pathogenic cycle between Dectin‐1 activation and hepatitis progression. In vivo administration of the fraction into mice induced hepatic inflammation. These results highlight a role of self‐recognition through Dectin‐1 that triggers hepatic innate immune responses and contributes to the exacerbation of inflammation in pathogenic settings. Thus, the blockade of this axis may provide a therapeutic option for liver inflammatory diseases.