title: Type I interferon modulates monocyte recruitment and maturation in chronic inflammation.
abstract: Chronic inflammation is characterized by continuous recruitment and activation of immune cells such as monocytes in response to a persistent stimulus. Production of proinflammatory mediators by monocytes leads to tissue damage and perpetuates the inflammatory response. However, the mechanism(s) responsible for the sustained influx of monocytes in chronic inflammation are not well defined. In chronic peritonitis induced by pristane, the persistent recruitment of Ly6C(hi) inflammatory monocytes into the peritoneum was abolished in type I interferon (IFN-I) receptor-deficient mice but was unaffected by the absence of IFN-gamma, tumor necrosis factor-alpha, interleukin-6, or interleukin-1. IFN-I signaling stimulated the production of chemokines (CCL2, CCL7, and CCL12) that recruited Ly6C(hi) monocytes via interactions with the chemokine receptor CCR2. Interestingly, after 2,6,10,14-tetramethylpentadecane treatment, the rapid turnover of inflammatory monocytes in the inflamed peritoneum was associated with a lack of differentiation into Ly6C(lo) monocytes/macrophages, a more mature subset with enhanced phagocytic capacity. In contrast, Ly6C(hi) monocytes differentiated normally into Ly6C(lo) cells in IFN-I receptor-deficient mice. The effects of IFN-I were specific for monocytes as granulocyte migration was unaffected in the absence of IFN-I signaling. Taken together, our findings reveal a novel role of IFN-I in promoting the recruitment of inflammatory monocytes via the chemokine receptor CCR2. Continuous monocyte recruitment and the lack of terminal differentiation induced by IFN-I may help sustain the chronic inflammatory response.
authors.affiliation: Center for Autoimmune Disease, University of Florida, Gainesville, 32610-0221, USA. puilee05@ufl.edu
authors.forename: Pui Y
authors.initials: PY
authors.lastname: Lee
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Yutaro
authors.initials: Y
authors.lastname: Kumagai
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.forename: Erinn S
authors.initials: ES
authors.lastname: Kellner
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Butfiloski
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Eric S
authors.initials: ES
authors.lastname: Sobel
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007249:Inflammation / Q000276:immunology*; D007370:Interferon Type I / Q000235:genetics / Q000276:immunology*; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology; D054390:Receptors, CCR2 / Q000235:genetics / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C515335:Ccr2 protein, mouse; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D015850:Interleukin-6; D054390:Receptors, CCR2; D017472:Receptors, Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D053633:Receptor, Interferon alpha-beta