Molecular mechanism of tissue fibrosis and develpment of revolutionary anti-fibrotic therapy

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Fibrosis is a final, common pathological outcome of a variety of chronic inflammatory diseases. In this study, we focused on Macrophage-inducible C-type lectin (Mincle), a pathogen sensor that recognizes Mycobacterium tuberculosis and is induced in obese adipose tissue and investigated the role of Mincle in the regulation of adipose tissue fibrosis. In the obese adipose tissue, Mincle was expressed mainly in proinflammatory M1 macrophages. Mincle stimulation caused the upregulation of genes related to fibrogenesis in peritoneal macrophages. Furthermore, Mincle stimulation by trehalose 6,6'-dimycolate, an exogenous ligand for Mincle, in adipose tissue resulted in adipose tissue fibrosis. These observations suggest that Mincle activation in obese adipose tissue leads to the progression of adipose tissue fibrosis, thereby suggesting that Mincle antagonism offers an novel anti-fibrotic therapy for chronic fibrotic diseases.