TY - JOUR TI - Critical role of synovial tissue–resident macrophage niche in joint homeostasis and suppression of chronic inflammation AU - Huang, Qi-Quan AU - Doyle, Renee AU - Chen, Shang-Yang AU - Sheng, Qicong AU - Misharin, Alexander V. AU - Mao, Qinwen AU - Winter, Deborah R. AU - Pope, Richard M. T2 - Science Advances AB - 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. Using a novel model of rheumatoid arthritis, we identified a critical role for reduced tissue-resident macrophages. Using a novel model of rheumatoid arthritis, we identified a critical role for reduced tissue-resident macrophages. DA - 2021/01/01/ PY - 2021 DO - 10.1126/sciadv.abd0515 DP - advances.sciencemag.org VL - 7 IS - 2 SP - eabd0515 LA - en SN - 2375-2548 UR - https://advances.sciencemag.org/content/7/2/eabd0515 Y2 - 2021/01/08/20:17:14 ER -