ACKR2 limits skin fibrosis and hair loss through IFN-β

Sergei Butenko, Nofar Ben Jashar, Tsofiya Sheffer, Edmond Sabo, Sagie Schif-Zuck, Amiram Ariel

Research output: Contribution to journalArticlepeer-review


The resolution of inflammation facilitates proper wound healing and limits tissue repair short of exaggerated fibrotic scarring. The atypical chemokine receptor (ACKR)2/D6 scavenges inflammatory chemokines, while IFN-β is a recently unveiled pro-resolving cytokine. Both effector molecules limit acute inflammatory episodes and promote their resolution in various organs. Here, we found fibrotic skin lesions from ACKR2−/− mice presented increased epidermal and dermal thickening, atrophy of the subcutaneous adipose tissue, augmented disorientation of collagen deposition, and enhanced deformation and loss of hair follicles compared to WT counterparts. In addition, affected skin sections from ACKR2−/− mice contained reduced levels of the pro-resolving mediators IFN-β and IL-10, but increased levels of the pro-inflammatory chemokines CCL2 and 3, the pro-fibrotic cytokine TGF-β, and the immune-stimulating cytokine IL-12. Notably, treatment with exogenous IFN-β rescued, at least in part, all the pro-fibrotic outcomes and lesion size in ACKR2−/− mice and promoted expression of the pro-resolving enzyme 12/15-lipoxygenase (LO) in both ACKR2−/− and WT mice. Moreover, Ifnb−/− mice displayed enhanced pro-fibrotic indices upon exposure to bleomycin. These findings suggest ACKR2 is an important mediator in limiting inflammatory skin fibrosis and acts via IFN-β production to promote the resolution of inflammation and minimize tissue scaring.

Original languageEnglish
Article numbere21917
JournalFASEB Journal
Issue number10
StatePublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 Federation of American Societies for Experimental Biology.


  • ACKR2
  • IFN-β
  • collagen deposition
  • resolving inflammation
  • skin fibrosis

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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