{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T14:44:26Z","timestamp":1793285066910,"version":"4.5.0"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>An integral component of the antiviral response, type I IFNs require regulation to modulate immune activation. We identify \u03b2-arrestin 2 as a key modulator of type I IFN in primary human macrophages, an essential component of the innate immune response. \u03b2-Arrestin 2 was selectively activated by CCL2\/CCR2 signaling, which induced a decrease in IFN-\u03b1, but not IFN-\u03b2 expression. Small interfering RNA knockdown of \u03b2-arrestin 2 demonstrated its role in IFNAR1 internalization, as well as STAT1 and IRF3 activation. As a result, cytokine responses were not propagated following HIV infection and TLR3 activation. However, remnants of IFN signaling remained intact, despite \u03b2-arrestin 2 activation, as IFN-\u03b2, IFN-\u03b3, IFN-\u03bb1, IRF7, TRAIL, and MxA expression were sustained. Similar effects of \u03b2-arrestin 2 on IFN signaling occurred in hepatocytes, suggesting that arrestins may broadly modulate IFN responses in multiple cell types. In summary, we identify a novel role of \u03b2-arrestin 2 as an integral regulator of type I IFN through its internalization of IFNAR1 and a subsequent selective loss of downstream IFN signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.1800598","type":"journal-article","created":{"date-parts":[[2018,11,30]],"date-time":"2018-11-30T21:39:16Z","timestamp":1543613956000},"page":"105-118","source":"Crossref","is-referenced-by-count":14,"title":["CCR2 Signaling Selectively Regulates IFN-\u03b1: Role of \u03b2-Arrestin 2 in IFNAR1 Internalization"],"prefix":"10.1093","volume":"202","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5029-2628","authenticated-orcid":false,"given":"Dionna W","family":"Williams","sequence":"first","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"},{"name":"Department of Clinical Pharmacology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-3141","authenticated-orcid":false,"given":"Lauren C","family":"Askew","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0653-6792","authenticated-orcid":false,"given":"Elonna","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janice E","family":"Clements","sequence":"additional","affiliation":[{"name":"Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"},{"name":"Department of Pathology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"},{"name":"Department of Neurology, Johns Hopkins University School of Medicine , Baltimore, MD 21205"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,1,1]]},"reference":[{"key":"2025030417555765800_r1","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1038\/icb.2012.9","article-title":"The interferons and their receptors--distribution and regulation","volume":"90","author":"de Weerd","year":"2012","journal-title":"Immunol. 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