Brown and colleagues have found that myeloid inhibitory C-type lectin-like receptor (MICL, also known as CLEC12A) negatively regulates neutrophil activation through the direct recognition of neutrophil extracellular traps (NETs). MICL acts as an inhibitory pattern-recognition receptor (PRR) for NET-associated DNA and can restrict neutrophil activation and the formation of positive-feedback inflammatory loops in settings of autoimmunity and infection.

Previously, the authors found that Micl−/− mice develop exaggerated, non-resolving joint inflammation in a model of collagen antibody-induced arthritis (CAIA), but did not identify the underlying mechanism. In the present study, they compared cell infiltrates in the joints of mice with CAIA and found a notable increase of neutrophils, but not other myeloid populations, in the joints of Micl−/− mice compared with wild-type mice. This increase in neutrophil infiltration was seen early in the disease, before the emergence of clinical differences. Neutrophils isolated from the joints (but not from the bone marrow or blood) of Micl−/− mice with CAIA showed an increased activated phenotype, and depletion of neutrophils from Micl−/− and wild-type mice with CAIA reduced disease severity to an equivalent level in both groups. Furthermore, the transfer of Micl−/− neutrophils to wild-type mice with CAIA exacerbated joint inflammation, whereas the transfer of wild-type neutrophils had no effect.