{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T06:01:16Z","timestamp":1779170476195,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T00:00:00Z","timestamp":1640131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Animal models for complex diseases are needed to position and analyze the function of interacting genes. Previous positional cloning identified Ncf1 and Clec4b to be major regulators of arthritis models in rats. Here, we investigate epistasis between Ncf1 and Clec4b, two major regulators of arthritis in rats. We find that Clec4b and Ncf1 exert an additive effect on arthritis given by their joint ability to regulate neutrophils. Both genes are highly expressed in neutrophils, together regulating neutrophil availability and their capacity to generate reactive oxygen species. Using a glycan array, we identify key ligands of Clec4b and demonstrate that Clec4b-specific stimulation triggers neutrophils into oxidative burst. Our observations highlight Clec4b as an important regulator of neutrophils and demonstrate how epistatic interactions affect the susceptibility to, and severity of, autoimmune arthritis.<\/jats:p>","DOI":"10.3390\/antiox11010012","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T10:24:52Z","timestamp":1640168692000},"page":"12","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Glycan Activation of Clec4b Induces Reactive Oxygen Species Protecting against Neutrophilia and Arthritis"],"prefix":"10.3390","volume":"11","author":[{"given":"Mike","family":"Aoun","sequence":"first","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojie","family":"Cai","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"},{"name":"Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingze","family":"Xu","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gonzalo Fernandez","family":"Lahore","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Yi","family":"Bonner","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0659-2150","authenticated-orcid":false,"given":"Yibo","family":"He","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liselotte","family":"B\u00e4ckdahl","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-2576","authenticated-orcid":false,"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Department Medical Biochemistry and Biophysics, Division Medical Inflammation Research, Karolinska Institute, 171 77 Stockholm, Sweden"},{"name":"The Second Affiliated Hospital of Xi\u2019an Jiaotong University, Xibei Hospital, Xi\u2019an 710004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1016\/S0140-6736(16)30173-8","article-title":"Rheumatoid arthritis","volume":"388","author":"Smolen","year":"2016","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/nature08494","article-title":"Finding the missing heritability of complex diseases","volume":"461","author":"Manolio","year":"2009","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1242\/dmm.026435","article-title":"Rheumatoid arthritis: Identifying and characterising polymorphisms using rat models","volume":"9","author":"Yau","year":"2016","journal-title":"Dis. 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