Rheumatoid arthritis (RA) is a complex autoimmune disease characterised by progressive joint destruction and systemic co-morbidities. Myeloid cells such as neutrophils can be found in abundance in the synovial fluid of patients and animal models of RA, where they release reactive-oxygen species (ROS), neutrophil extracellular traps (NETs) and other inflammatory mediators aiding the progression of joint destruction. CLEC12a (or MICL, Myeloid inhibitory C-type lectin), an inhibitory receptor expressed on myeloid cells, has previously been linked to the control of gouty arthritis through recognition of monosodium urate microcrystals (MSU). Here we demonstrate that CLEC12a is essential for the control of neutrophil activation and function in RA. Specifically, in the absence of CLEC12a, neutrophil migration to, and activation within the joint of CAIA mice is increased, leading to augmented NET formation and ultimately joint destruction. Antibody-mediated depletion of neutrophils ameliorated disease while inhibition of NETosis via chemical inhibition of PAD4 rescued the phenotype of KO mice. Notably, adoptive transfer of CLEC12a KO neutrophils into wild-type (WT) mice can transiently recapitulate the KO mice inflammatory defect. Thus, CLEC12a represents a novel autoregulatory pathway which prevents aberrant neutrophil activity, including NET formation and subsequent tissue damage in RA. While previous results did not find any association with polymorphisms in CLEC12a and RA, here we reveal that two-thirds of RA patients presented with autoantibodies against CLEC12a in their serum. Importantly, previous results suggest administration of anti-Clec12a antibodies to CAIA WT mice exacerbates disease. Mechanistically, we demonstrate here that antibody-blocking of CLEC12a on human neutrophils in vitro amplifies MSU-induced ROS generation as previously seen in KO murine neutrophils. Additionally, we have identified the presence of an inflammation-induced endogenous CLEC12a ligand in the joint. In conclusion, we present a novel mechanism whereby autoantibodies against CLEC12a in RA patients influence the neutrophil autoregulatory function of CLEC12a by interfering with the CLEC12a-ligand interaction, thus enabling disease progression in RA.