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It has been demonstrated that <jats:italic>CHRFAM7A<\/jats:italic> dominant negatively regulates the functions of \u03b17\u2010nAChR. However, its role in inflammation remains to be fully characterized. <jats:italic>CHRFAM7A<\/jats:italic> transgenic (Tg) mice were phenotypically normal and their peritoneal macrophages exhibited decreased ligand\u2010binding capability and, importantly, an activated gene expression profile of pro\u2010inflammatory cytokines. Surprisingly, when challenged with sepsis, the Tg mice showed no survival disadvantage relative to their wild\u2010type (Wt) counterparts. Further analysis showed that the complete blood count and serum levels of pro\u2010inflammatory cytokines were comparable at resting state, but the degrees of leukocyte mobilization and the increase of pro\u2010inflammatory cytokines were significantly higher in Tg than Wt mice at the early stage of sepsis. In vitro, peritoneal macrophages of the Tg mice exhibited an exaggerated response to lipopolysaccharides (LPSs), especially at the earlier time points and at lower dosages of LPS. Remarkably, monocytes from <jats:italic>CHRFAM7A<\/jats:italic>\u2010carrier showed similar dynamic changes of the pro\u2010inflammatory cytokines to that observed in the Tg mice upon LPS challenge. Our results suggest that <jats:italic>CHRFAM7A<\/jats:italic> increases the mobilization of leukocytes and primes macrophages that confer an enhanced immune response at the early stage of inflammation, which may lead to prompt pathogen clearance, an evolutionary advantage in less severe inflammatory conditions.<\/jats:p>","DOI":"10.1002\/cbin.12083","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T08:48:50Z","timestamp":1693558130000},"page":"1926-1941","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Human\u2010specific <i>CHRFAM7A<\/i> primes macrophages for a heightened pro\u2010inflammatory response at the earlier stage of inflammation"],"prefix":"10.1002","volume":"47","author":[{"given":"Rui","family":"Zhou","sequence":"first","affiliation":[{"name":"National Regional Children's Medical Center (Northwest), Key Laboratory of Precision Medicine to Pediatric Diseases of 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