Single-cell profiling identifies IL1Bhi macrophages associated with inflammation in PD-1 inhibitor-induced inflammatory arthritis

Ziyue Zhou, Xiaoxiang Zhou, Xu Jiang, Bo Yang, Xin Lu, Yunyun Fei, Lidan Zhao, Hua Chen, Li Zhang, Xiaoyan Si, Naixin Liang, Yadong Wang, Dan Yang, Yezi Peng, Yiying Yang, Zhuoran Yao, Yangzhige He, Xunyao Wu, Wen Zhang, Min Wang, Huaxia Yang () and Xuan Zhang ()
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Ziyue Zhou: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaoxiang Zhou: Chinese Academy of Medical Sciences and Peking Union Medical College
Xu Jiang: Chinese Academy of Medical Sciences and Peking Union Medical College
Bo Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Xin Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Yunyun Fei: Chinese Academy of Medical Sciences and Peking Union Medical College
Lidan Zhao: Chinese Academy of Medical Sciences and Peking Union Medical College
Hua Chen: Chinese Academy of Medical Sciences and Peking Union Medical College
Li Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Xiaoyan Si: Chinese Academy of Medical Sciences and Peking Union Medical College
Naixin Liang: Chinese Academy of Medical Sciences
Yadong Wang: Chinese Academy of Medical Sciences
Dan Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Yezi Peng: Chinese Academy of Medical Sciences and Peking Union Medical College
Yiying Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Zhuoran Yao: Sichuan University
Yangzhige He: Chinese Academy of Medical Sciences and Peking Union Medical College
Xunyao Wu: Chinese Academy of Medical Sciences and Peking Union Medical College
Wen Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Min Wang: Chinese Academy of Medical Sciences
Huaxia Yang: Chinese Academy of Medical Sciences and Peking Union Medical College
Xuan Zhang: Chinese Academy of Medical Sciences

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45+ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1Bhi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1Bhi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1Bhi monocytes. Exhausted CD8+ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1Bhi myeloid cells communicated with CD8+ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1Bhi macrophages as a possible therapeutic target in PD-1-IA.

Date: 2024
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DOI: 10.1038/s41467-024-46195-x

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