Open AccessCritical role of synovial tissue–resident macrophage niche in joint homeostasis and suppression of chronic inflammation
Author(s) -
Qi Huang,
Renee Doyle,
Shang-Yang Chen,
Qicong Sheng,
Alexander V. Misharin,
Qinwen Mao,
Deborah R. Winter,
Richard M. Pope
Publication year - 2021
Publication title -
science advances
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.928
H-Index - 146
ISSN - 2375-2548
DOI - 10.1126/sciadv.abd0515
Subject(s) - inflammation , rheumatoid arthritis , immunology , macrophage , monocyte , arthritis , cd11c , synovial membrane , homeostasis , synovitis , medicine , biology , pathology , microbiology and biotechnology , phenotype , biochemistry , gene , in vitro
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.