期刊
SCIENCE ADVANCES
卷 7, 期 2, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abd0515
关键词
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资金
- NIH [R01AR070025, AR048269, HL135124, AG049665, AI135964]
- Solovy/Arthritis Research Society Endowment
- Arthritis National Research Foundation
- American Lung Association [514724]
- Scleroderma Foundation
- American Federation for Aging
- American Heart Association [18CDA34110224]
- ATS Foundation/Mallinckrodt Pharmaceuticals Research Fellowship
- Department of Defense [PR141319]
Analysis of a novel mouse model of rheumatoid arthritis reveals the importance of the macrophage tissue-resident niche in suppressing chronic inflammation, potentially contributing to the pathogenesis of rheumatoid arthritis.
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 F4/80(int) and self-renewing F4/80(hi) 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 F4/80(hi) 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 F4/80(hi) 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.
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