関節マクロファージの炎症惹起機構を解明―関節リウマチの新たな治療法開発に期待―

2026-03-26 京都大学

骨髄から血液中を移動してきた炎症性単球は関節に入るとGM-CSFの作用を受けてArg1⁺およびEpCAM⁺マクロファージに分化し関節の炎症増幅に関わる。特にEpCAM⁺マクロファージはCCL17を介して痛みにも関わっている。（作者：向山宙希）

＜関連情報＞

• https://www.kyoto-u.ac.jp/ja/research-news/2026-03-26
• https://www.kyoto-u.ac.jp/sites/default/files/2026-03/web_2603_Mukoyama-8050f7e9001882a8c2c1b9656ab03588.pdf
• https://www.science.org/doi/10.1126/sciadv.aec0986

GM-CSFは自己免疫性関節炎において炎症性マクロファージの機能的多様化をもたらす Pathogenic GM-CSF drives functional diversification of inflammatory macrophages in autoimmune arthritis

Hiroki Mukoyama, Yusuke Takeuchi, Daiya Ohara, Yoonha Lee, […] , and Keiji Hirota
Science Advances  Published:25 Mar 2026
DOI:https://doi.org/10.1126/sciadv.aec0986

Abstract

Autoimmune T cells orchestrate joint inflammation and pain in concert with synovial macrophages; however, the mechanisms governing the development and functional diversification of these macrophages remain unclear. Using a model of T helper 17 cell (T_H17 cell)–mediated autoimmune arthritis, we show that joint-infiltrating Ly6C^hi monocytes in response to autoimmune T_H17 cells, rather than resident synovial macrophages, are the primary mediators of disease pathogenesis. Granulocyte-macrophage colony-stimulating factor (GM-CSF), a critical component of the pathogenic circuit driven by arthritogenic T_H17 cells, does not contribute to monocyte recruitment to the synovium but facilitates their subsequent differentiation into functionally distinct synovial macrophage subsets, thereby amplifying joint inflammation. Single-cell RNA sequencing identified two GM-CSF–dependent subpopulations of pathogenic synovial macrophages—Arginase-1⁺ and epithelial cell adhesion molecule (EpCAM)⁺ clusters—both expressing proinflammatory cytokines and matrix metalloproteinases. Notably, EpCAM⁺ macrophages uniquely express Ccl17, a pronociceptive mediator implicated in arthritic pain. Collectively, these findings delineate a GM-CSF–driven program of macrophage diversification that underpins both joint inflammation and pain, implicating this axis in the chronic activation of inflammatory and nociceptive pathways in autoimmune arthritis.