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To eradicate pathogens and contribute to tissue repair, recruited neutrophils generate and release a host of toxic chemicals that can also damage normal cells. To avoid collateral damage leading to tissue injury and organ dysfunction, molecular mechanisms evolved that tightly control neutrophil response threshold to activating signals, the strength and location of the response, and the timing of response termination. One mechanism of response control is interruption of activating intracellular signaling pathways by the 20 inhibitory receptors expressed by neutrophils. The two inhibitory C\u2010type lectin receptors expressed by neutrophils, CLEC12A and DCIR, exhibit both common and distinct molecular and functional mechanisms, and they are associated with different diseases. In this review, we use studies on CLEC12A as a model of inhibitory receptor regulation of neutrophil function and participation in disease. Understanding the molecular mechanisms leading to inhibitory receptor specificity offers the possibility of using physiologic control of neutrophil functions as a pharmacologic tool to control inflammatory diseases.<\/jats:p>","DOI":"10.1111\/imr.13174","type":"journal-article","created":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T07:09:46Z","timestamp":1669360186000},"page":"50-68","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Understanding inhibitory receptor function in neutrophils through the lens of <scp>CLEC12A<\/scp>"],"prefix":"10.1111","volume":"314","author":[{"given":"Kenneth R.","family":"McLeish","sequence":"first","affiliation":[{"name":"Department of Medicine University of Louisville School of Medicine  Louisville Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-025X","authenticated-orcid":false,"given":"Maria 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