Positive and negative regulation of the Fcγ receptor–stimulating activity of RNA-containing immune complexes by RNase

Naito, Ryota; Ohmura, Koichiro; Higuchi, Shuhei et al.

JCI Insight, 2023, 8(16), e167799

Number of Access:217（2025-09-11 12:59 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/93235

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Title
Positive and negative regulation of the Fcγ receptor–stimulating activity of RNA-containing immune complexes by RNase
Creator
CreatorName
Naito, Ryota
NRID
1000040432372 1000040432372
CreatorName
Ohmura, Koichiro
CreatorName
Higuchi, Shuhei
CreatorName
Nakai, Wataru
NRID
1000070311339 1000070311339
researchmap permalink
MKohyama MKohyama
Scopus Author ID
7005073030 7005073030
CreatorName
Kohyama, Masako
NRID
1000010157589 1000010157589
CreatorName
Mimori, Tsuneyo
NRID
1000010294216 1000010294216
CreatorName
Morinobu, Akio
NRID
1000010261900 1000010261900
ORCID
0000-0002-1153-3166 0000-0002-1153-3166
researchmap permalink
read0187233 read0187233
Scopus Author ID
7006548315 7006548315
CreatorName
Arase, Hisashi
Description
Naito R., Ohmura K., Higuchi S., et al. Positive and negative regulation of the Fcγ receptor–stimulating activity of RNA-containing immune complexes by RNase. JCI Insight 8, e167799 (2023); https://doi.org/10.1172/jci.insight.167799.
Abstract
The U1RNP complex, Ro/SSA, and La/SSB are major RNA-containing autoantigens. Immune complexes (ICs) composed of RNA-containing autoantigens and autoantibodies are suspected to be involved in the pathogenesis of some systemic autoimmune diseases. Therefore, RNase treatment, which degrades RNA in ICs, has been tested in clinical trials as a potential therapeutic agent. However, no studies to our knowledge have specifically evaluated the effect of RNase treatment on the Fcγ receptor–stimulating (FcγR-stimulating) activity of RNA-containing ICs. In this study, using a reporter system that specifically detects FcγR-stimulating capacity, we investigated the effect of RNase treatment on the FcγR-stimulating activity of RNA-containing ICs composed of autoantigens and autoantibodies from patients with systemic autoimmune diseases such as systemic lupus erythematosus. We found that RNase enhanced the FcγR-stimulating activity of Ro/SSA- and La/SSB-containing ICs, but attenuated that of the U1RNP complex–containing ICs. RNase decreased autoantibody binding to the U1RNP complex, but increased autoantibody binding to Ro/SSA and La/SSB. Our results suggest that RNase enhances FcγR activation by promoting the formation of ICs containing Ro/SSA or La/SSB. Our study provides insights into the pathophysiology of autoimmune diseases involving anti-Ro/SSA and anti-La/SSB autoantibodies, and into the therapeutic application of RNase treatment for systemic autoimmune diseases.
Publisher
American Society for Clinical Investigation
Source Title
JCI Insight
Volume (Issue)
8(16)
Page
e167799
Date of Issued
2023-08-22
Language
English
Handle URL
https://hdl.handle.net/11094/93235
eISSN
23793708
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1172/jci.insight.167799
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
oaire:version
Version of Record
Category
学術雑誌論文 Journal Article