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In infection with Nippostrongylus brasiliensis (Nb), RELM\u03b1 dampens Th2 inflammatory responses. RELM\u03b1 is expressed by immune cells, and by epithelial cells (EC); however, the functional impact of immune versus EC-derived RELM\u03b1 is unknown. We generated bone marrow (BM) chimeras that were RELM\u03b1 deficient (RELM\u03b1\u2212\/\u2212) in BM or non BM cells and infected them with Nb. Non BM RELM\u03b1\u2212\/\u2212 chimeras had comparable inflammatory responses and parasite burdens to RELM\u03b1+\/+ mice. In contrast, both RELM\u03b1\u2212\/\u2212 and BM RELM\u03b1\u2212\/\u2212 mice exhibited increased Nb-induced lung and intestinal inflammation, correlated with elevated Th2 cytokines and Nb killing. CD11c+ lung macrophages were the dominant BM-derived source of RELM\u03b1 and can mediate Nb killing. Therefore, we employed a macrophage-worm co-culture system to investigate whether RELM\u03b1 regulates macrophage-mediated Nb killing. Compared to RELM\u03b1+\/+ macrophages, RELM\u03b1\u2212\/\u2212 macrophages exhibited increased binding to Nb and functionally impaired Nb development. Supplementation with recombinant RELM\u03b1 partially reversed this phenotype. Gene expression analysis revealed that RELM\u03b1 decreased cell adhesion and Fc receptor signaling pathways, which are associated with macrophage-mediated helminth killing. Collectively, these studies demonstrate that BM-derived RELM\u03b1 is necessary and sufficient to dampen Nb immune responses, and identify that one mechanism of action of RELM\u03b1 is through inhibiting macrophage recruitment and interaction with Nb. Our findings suggest that RELM\u03b1 acts as an immune brake that provides mutually beneficial effects for the host and parasite by limiting tissue damage and delaying parasite expulsion.<\/jats:p>\n               <jats:p>Employing hookworm infection of RELM\u03b1\u2212\/\u2212 bone marrow chimeras, co-culture assays, and gene expression analysis, we show that lung macrophage-derived RELM\u03b1 downregulates inflammation and parasite killing.<\/jats:p>","DOI":"10.1002\/jlb.4a0917-369rr","type":"journal-article","created":{"date-parts":[[2018,7,11]],"date-time":"2018-07-11T03:31:34Z","timestamp":1531279894000},"page":"855-869","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Hematopoietic cell-derived RELM\u03b1 regulates hookworm immunity through effects on macrophages"],"prefix":"10.1093","volume":"104","author":[{"given":"Hashini M","family":"Batugedara","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dihong","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Nematology, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay J","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica C","family":"Jang","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly C","family":"Radecki","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail C","family":"Burr","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David D","family":"Lo","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adler R","family":"Dillman","sequence":"additional","affiliation":[{"name":"Department of Nematology, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meera G","family":"Nair","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, University of California Riverside , Riverside, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2018,7,10]]},"reference":[{"key":"2023032406120906200_jlb10197-cit-0001","doi-asserted-by":"crossref","first-page":"5513","DOI":"10.1073\/pnas.88.13.5513","article-title":"Interleukin 4 is important in protective immunity to a gastrointestinal nematode infection in mice","volume":"88","author":"Urban","year":"1991","journal-title":"Proc Natl Acad Sci U S 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