Self‐recognition through Dectin‐1 exacerbates liver inflammation

Abstract Dectin‐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 CCl 4 ‐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.