Type I Interferon Modulates Monocyte Recruitment and Maturation in Chronic Inflammation

P.Y. Lee, Y. Li, Y. Kumagai, Y. Xu, J.S. Weinstein, E.C. Kellner, D.G. Nacionales, E.J. Butfiloski, N. van Rooijen, S Akira, E.S. Sobel, M. Satoh, W.H. Reeves

Research output: Contribution to journalArticleAcademicpeer-review

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. (Am J Pathol 2009, 175:2023-2033; DOI: 10.2353/ajpath.2009.090328)
Original languageUndefined/Unknown
Pages (from-to)2023-2033
JournalThe American Journal of Pathology
Volume175
Issue number5
DOIs
Publication statusPublished - 2009

Cite this

Lee, P. Y., Li, Y., Kumagai, Y., Xu, Y., Weinstein, J. S., Kellner, E. C., ... Reeves, W. H. (2009). Type I Interferon Modulates Monocyte Recruitment and Maturation in Chronic Inflammation. The American Journal of Pathology, 175(5), 2023-2033. https://doi.org/10.2353/ajpath.2009.090328