Critical role of synovial tissue–resident macrophage niche in joint homeostasis and suppression of chronic inflammation
Open Access
- 8 January 2021
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 7 (2), eabd0515
- https://doi.org/10.1126/sciadv.abd0515
Abstract
Little is known about the mechanisms regulating the transition of circulating monocytes into pro- or anti-inflammatory macrophages in chronic inflammation. Here, we took advantage of our novel mouse model of rheumatoid arthritis, in which Flip is deleted under the control of a CD11c promoter (HUPO mice). During synovial tissue homeostasis, both monocyte-derived F4/80int and self-renewing F4/80hi tissue–resident, macrophage populations were identified. However, in HUPO mice, decreased synovial tissue–resident macrophages preceded chronic arthritis, opened a niche permitting the influx of activated monocytes, with impaired ability to differentiate into F4/80hi tissue–resident macrophages. In contrast, Flip-replete monocytes entered the vacated niche and differentiated into tissue-resident macrophages, which suppressed arthritis. Genes important in macrophage tissue residency were reduced in HUPO F4/80hi macrophages and in leukocyte-rich rheumatoid arthritis synovial tissue monocytes. Our observations demonstrate that the macrophage tissue–resident niche is necessary for suppression of chronic inflammation and may contribute to the pathogenesis of rheumatoid arthritis.Funding Information
- U.S. Department of Defense (PR141319)
- NIH Office of the Director (R01AR070025)
- NIH Office of the Director (HL135124)
- NIH Office of the Director (HL135124)
- NIH Office of the Director (AG049665)
- American College of Rheumatology Research and Education Foundation (AR048269)
- American Federation for Aging Research
- American Heart Association (18CDA34110224)
- Scleroderma Foundation
- American Lung Association (514724)
- National Research Foundation
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