Remodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice

Shengchang Zhang, Ying Liu, Weiqiang Jing, Qihao Chai, Chunwei Tang, Ziyang Li, Zhentao Man, Chen Chen, Jing Zhang, Peng Sun, Rui Zhang, Zhenmei Yang, Maosen Han, Yan Wang, Xia Wei, Jun Li, Wei Li, Mohnad Abdalla, Gongchang Yu, Bin Shi, Yuankai Zhang (), Kun Zhao and Xinyi Jiang ()
Additional contact information
Shengchang Zhang: Shandong University
Ying Liu: Shandong University
Weiqiang Jing: Qilu Hospital, Cheeloo College of Medicine, Shandong University
Qihao Chai: Shandong Provincial Hospital Affiliated to Shandong University
Chunwei Tang: Shandong University
Ziyang Li: Qilu Hospital, Cheeloo College of Medicine, Shandong University
Zhentao Man: Shandong Provincial Hospital Affiliated to Shandong University
Chen Chen: Shandong University
Jing Zhang: Shandong University
Peng Sun: Shandong University of Traditional Chinese Medicine
Rui Zhang: Shandong University
Zhenmei Yang: Shandong University
Maosen Han: Shandong University
Yan Wang: Shandong University
Xia Wei: Shandong Institute for Food and Drug Control
Jun Li: Shandong Institute for Food and Drug Control
Wei Li: Shandong Provincial Hospital Affiliated to Shandong University
Mohnad Abdalla: Shandong University
Gongchang Yu: Shandong First Medical University & Shandong Academy of Medical Sciences
Bin Shi: Shandong First Medical University & Shandong Academy of Medical Sciences
Yuankai Zhang: Qilu Hospital, Cheeloo College of Medicine, Shandong University
Kun Zhao: Shandong University
Xinyi Jiang: Shandong University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Massive intra-articular infiltration of proinflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular immune dysfunction, severe synovitis and ultimately joint erosion. Here we report an efferocytosis-informed nanoimitator (EINI) for in situ targeted reprogramming of synovial inflammatory macrophages (SIMs) that thwarts their autoimmune attack and reestablishes articular immune homeostasis, which mitigates RA. The EINI consists of a drug-based core with an oxidative stress-responsive phosphatidylserine (PtdSer) corona and a shell composed of a P-selectin-blocking motif, low molecular weight heparin (LMWH). When systemically administered, the LMWH on the EINI first binds to P-selectin overexpressed on the endothelium in subsynovial capillaries, which functions as an antagonist, disrupting neutrophil synovial trafficking. Due to the strong dysregulation of the synovial microvasculature, the EINI is subsequently enriched in the joint synovium where the shell is disassembled upon the reactive oxygen species stimulation, and PtdSer corona is then exposed. In an efferocytosis-like manner, the PtdSer-coroneted core is in turn phagocytosed by SIMs, which synergistically terminate SIM-initiated pathological cascades and serially reestablish intra-articular immune homeostasis, conferring a chondroprotective effect. These findings demonstrate that SIMs can be precisely remodeled via the efferocytosis-mimetic strategy, which holds potential for RA treatment.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-36468-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36468-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-36468-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().