Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance

Yamada, Shûzô; Nagafuchi, Yasuo; Wang, Min; M, Ota; Hatano, Hiroaki; Takeshima, Yusuke; Okubo, Masaaki; Kobayashi, Satomi; Sugimori, Yusuke; Nakano, Masaaki; Yoshida, Ryochi; Hanata, Norio; Suwa, Yuichi; Tsuchida, Yoshiaki; Iwasaki, Yukiko; Sumitomo, Shuji; Kubo, Kanae; Shimane, Kenichi; Setoguchi, Keigo; Azuma, Takanori; Kanda, Hiroko; Shoda, Hirofumi; Zhang, Xuan; Yamamoto, Kazuhiko; Ishigaki, Kazuyoshi; Okamura, Tomohisa; Fujio, Keishi

doi:10.1101/2022.12.21.22283652

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…Dendritic cells are mainly known as plasmacytoid dendritic cells and myeloid dendritic cells (mDCs), but few studies have focused on dendritic cells in RA synovial tissues 21 . Our CD14+ dendritic‐shaped cells may be the equivalent of mDCs, but their generation and differentiation have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

CD14+ Dendritic‐Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues

Kurose,

Satoh,

Kurose

et al. 2024

ACR Open Rheumatology

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ObjectiveWe previously reported that CD14+ dendritic‐shaped cells exhibit a dendritic morphology, engage in pseudo‐emperipolesis with lymphocytes, and express CD90 in the perivascular areas of rheumatoid arthritis (RA) synovial tissues. However, it remains unclear whether these CD14highCD90intermediate(int) cells function as dendritic cells. In this study, we investigated the dendritic cell–differentiation potential of CD14highCD90int cells.MethodsThe localization and number of CD14highCD90int cells in RA synovial tissues and peripheral blood were examined. The dendritic cell–differentiation potential of CD14highCD90int cells was examined by measuring interleukin‐6 and tumor necrosis factor‐α levels in the supernatant and CD83 and human leukocyte antigen (HLA)‐DR expression in the cells after induction of dendritic cell differentiation. Synovial cells were co‐cultured with lymphocytes, and the activation of these cells was examined.ResultsCD14highCD90int cells were abundant in RA synovial tissues, including the sublining layer and the pannus areas. Patients with untreated and active RA had significantly higher percentages of CD14highCD90int cells in the peripheral blood and synovial tissues. In RA synovial cells, inflammatory cytokine levels increased with dendritic cell–differentiation culture, but CD83 and HLA‐DR expression were significantly increased in the CD14highCD90int cell group. When co‐cultured with lymphocytes, cell numbers and inflammatory cytokine levels significantly increased in both groups of synovial cells after dendritic cell induction.ConclusionCD14+ cells migrate and spread from the circulating blood to RA synovial tissues while expressing CD90, and CD14highCD90int cells in contact with lymphocytes differentiate into HLA‐DR+ dendritic cells, which contribute to chronic inflammation in RA.

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Section: Discussionmentioning

confidence: 99%

CD14+ Dendritic‐Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues

Kurose,

Satoh,

Kurose

et al. 2024

ACR Open Rheumatology

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“…Also DCs, a subtype of the myeloid lineage with specialised antigen-presenting capabilities, are importantly involved in the inflammatory remodelling of tissue during arthritis and SSc and seem to be good predictors for disease progression and clinical treatment response 163–165. scRNA-Seq and functional analyses have revealed several subtypes of DCs in the RA synovium and organs affected by SSc 120 165 166.…”

Section: Cellular Players In Inflammatory Maladaptation Of Tissuesmentioning

confidence: 99%

Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases

Hoffmann,

Kirchner,

Krönke

et al. 2024

Annals of the Rheumatic Diseases

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Due to optimised treatment strategies and the availability of new therapies during the last decades, formerly devastating chronic inflammatory diseases such as rheumatoid arthritis or systemic sclerosis (SSc) have become less menacing. However, in many patients, even state-of-the-art treatment cannot induce remission. Moreover, the risk for flares strongly increases once anti-inflammatory therapy is tapered or withdrawn, suggesting that underlying pathological processes remain active even in the absence of overt inflammation. It has become evident that tissues have the ability to remember past encounters with pathogens, wounds and other irritants, and to react more strongly and/or persistently to the next occurrence. This priming of the tissue bears a paramount role in defence from microbes, but on the other hand drives inflammatory pathologies (the Dr Jekyll and Mr Hyde aspect of tissue adaptation). Emerging evidence suggests that long-lived tissue-resident cells, such as fibroblasts, macrophages, long-lived plasma cells and tissue-resident memory T cells, determine inflammatory tissue priming in an interplay with infiltrating immune cells of lymphoid and myeloid origin, and with systemically acting factors such as cytokines, extracellular vesicles and antibodies. Here, we review the current state of science on inflammatory tissue priming, focusing on tissue-resident and tissue-occupying cells in arthritis and SSc, and reflect on the most promising treatment options targeting the maladapted tissue response during these diseases.

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The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

Zhao,

He,

Zhao

et al. 2023

Front. Immunol.

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Angiogenesis plays a key role in the pathological process of inflammation and invasion of the synovium, and primarily drives the progression of rheumatoid arthritis (RA). Recent studies have demonstrated that the Notch signaling may represent a new therapeutic target of RA. Although the Notch signaling has been implicated in the M1 polarization of macrophages and the differentiation of lymphocytes, little is known about its role in angiogenesis in RA. In this review, we discourse the unique roles of stromal cells and adipokines in the angiogenic progression of RA, and investigate how epigenetic regulation of the Notch signaling influences angiogenesis in RA. We also discuss the interaction of the Notch-HIF signaling in RA’s angiogenesis and the potential strategies targeting the Notch signaling to improve the treatment outcomes of RA. Taken together, we further suggest new insights into future research regarding the challenges in the therapeutic strategies of RA.

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Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance

Cited by 4 publications

References 42 publications

CD14+ Dendritic‐Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues

CD14+ Dendritic‐Shaped Cells Functioning as Dendritic Cells in Rheumatoid Arthritis Synovial Tissues

Inflammatory tissue priming: novel insights and therapeutic opportunities for inflammatory rheumatic diseases

The Notch signaling-regulated angiogenesis in rheumatoid arthritis: pathogenic mechanisms and therapeutic potentials

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