Non-classical monocytes as mediators of tissue destruction in arthritis

Antonia Puchner, Victoria Saferding, Michael Bonelli, Yohei Mikami, Melanie Hofmann, Julia S. Brunner, Michael Caldera, Eliana Goncalves-Alves, Nikolaus B. Binder, Anita Fischer, Elisabeth Simader, Carl Walter Steiner, Harald Leiss, Silvia Hayer, Birgit Niederreiter, Thomas Karonitsch, Marije I. Koenders, Bruno K. Podesser, John J. O'Shea, Jörg MencheJosef S. Smolen, Kurt Redlich, Stephan Blüml

研究成果: Article査読

33 被引用数 (Scopus)

抄録

Objectives: Bone destruction in rheumatoid arthritis is mediated by osteoclasts (OC), which are derived from precursor cells of the myeloid lineage. The role of the two monocyte subsets, classical monocytes (expressing CD115, Ly6C and CCR2) and non-classical monocytes (which are CD115 positive, but low in Ly6C and CCR2), in serving as precursors for OC in arthritis is still elusive. Methods: We investigated CCR2'/ mice, which lack circulating classical monocytes, crossed into hTNFtg mice for the extent of joint damage. We analysed monocyte subsets in hTNFtg and K/BxN serum transfer arthritis by flow cytometry. We sorted monocyte subsets and analysed their potential to differentiate into OC and their transcriptional response in response to RANKL by RNA sequencing. With these data, we performed a gene ontology enrichment analysis and gene set enrichment analysis. Results: We show that in hTNFtg arthritis local bone erosion and OC generation are even enhanced in the absence of CCR2. We further show the numbers of non-classical monocytes in blood are elevated and are significantly correlated with histological signs of joint destruction. Sorted non-classical monocytes display an increased capacity to differentiate into OCs. This is associated with an increased expression of signal transduction components of RANK, most importantly TRAF6, leading to an increased responsiveness to RANKL. Conclusion: Therefore, non-classical monocytes are pivotal cells in arthritis tissue damage and a possible target for therapeutically intervention for the prevention of inflammatory joint damage.

本文言語English
ジャーナルAnnals of the rheumatic diseases
DOI
出版ステータスAccepted/In press - 2018 6月 29
外部発表はい

ASJC Scopus subject areas

  • 免疫アレルギー学
  • リウマチ学
  • 免疫学
  • 生化学、遺伝学、分子生物学(全般)

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