CCR2 signaling selectively regulates IFN-α: Role of β-arrestin 2 in IFNAR1 internalization

Dionna W. Williams, Lauren C. Askew, Elonna Jones, Janice E. Clements

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


An integral component of the antiviral response, type I IFNs require regulation to modulate immune activation. We identify β-arrestin 2 as a key modulator of type I IFN in primary human macrophages, an essential component of the innate immune response. β-Arrestin 2 was selectively activated by CCL2/CCR2 signaling, which induced a decrease in IFN-α, but not IFN-β expression. Small interfering RNA knockdown of β-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 β-arrestin 2 activation, as IFN-β, IFN-γ, IFN-λ1, IRF7, TRAIL, and MxA expression were sustained. Similar effects of β-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 β-arrestin 2 as an integral regulator of type I IFN through its internalization of IFNAR1 and a subsequent selective loss of downstream IFN signaling.

Original languageEnglish (US)
Pages (from-to)105-118
Number of pages14
JournalJournal of Immunology
Issue number1
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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