The C-type lectin receptor Dectin-2 is crucial for the development of experimental autoimmune skin disease

Autoimmune blistering skin diseases have deleterious effects on patients’ lives with a great (and unmet) need for more treatment options and potential new drug targets. C-type lectin receptors like Dectin-2 are pattern recognition receptors that bind to carbohydrate moieties on microorganisms leading to the elimination of the pathogens. Recently, Dectin-2 gene variants have been linked to autoimmune diseases, its expression in neutrophils has been shown to be upregulated in the autoimmune blistering skin disease epidermolysis bullosa acquisita (EBA), while we found that immune complex-stimulated neutrophils upregulated the gene of Dectin-2. These results prompted us to test the role of Dectin-2 in neutrophil- and autoantibody-mediated experimental inflammation. Dectin-2-deficient mice showed a nearly complete protection against the development of EBA, which was further validated in the reverse passive Arthus reaction. Immune cell accumulation and proinflammatory mediator levels were also decreased in Dectin-2 –/– mice. In line with these findings, postmigratory Fc receptor-dependent neutrophil, but not macrophage functions were dramatically reduced in the absence of Dectin-2. Our results show an essential role for Dectin-2 in immune complex-mediated in vitro neutrophil processes, in experimental EBA and immune complex-mediated inflammation, which raise the possibility that this C-type lectin receptor could be a treatment target in these disorders.