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

© 2024. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:15

Enthalten in:

Nature communications - 15(2024), 1 vom: 07. März, Seite 2107

Sprache:

Englisch

Beteiligte Personen:

Zhou, Ziyue [VerfasserIn]
Zhou, Xiaoxiang [VerfasserIn]
Jiang, Xu [VerfasserIn]
Yang, Bo [VerfasserIn]
Lu, Xin [VerfasserIn]
Fei, Yunyun [VerfasserIn]
Zhao, Lidan [VerfasserIn]
Chen, Hua [VerfasserIn]
Zhang, Li [VerfasserIn]
Si, Xiaoyan [VerfasserIn]
Liang, Naixin [VerfasserIn]
Wang, Yadong [VerfasserIn]
Yang, Dan [VerfasserIn]
Peng, Yezi [VerfasserIn]
Yang, Yiying [VerfasserIn]
Yao, Zhuoran [VerfasserIn]
He, Yangzhige [VerfasserIn]
Wu, Xunyao [VerfasserIn]
Zhang, Wen [VerfasserIn]
Wang, Min [VerfasserIn]
Yang, Huaxia [VerfasserIn]
Zhang, Xuan [VerfasserIn]

Links:

Volltext

Themen:

IL1B protein, human
Immune Checkpoint Inhibitors
Interleukin-1beta
Journal Article
Programmed Cell Death 1 Receptor

Anmerkungen:

Date Completed 11.03.2024

Date Revised 11.03.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-024-46195-x

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM369436547