Evidence map›Paper›PMID 34907668›Full record

ArticleArthritis & rheumatology (Hoboken, N.J.)2022

CD163+ M2 Macrophages Promote Fibrosis in IgG4-Related Disease Via Toll-like Receptor 7/Interleukin-1 Receptor-Associated Kinase 4/NF-κB Signaling.

Akira Chinju, Masafumi Moriyama, Noriko Kakizoe-Ishiguro, Hu Chen, Yuka Miyahara, A S M Rafiul Haque, Katsuhiro Furusho, Mizuki Sakamoto, Kazuki Kai, Kotono Kibe and 4 more

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In one paragraph

Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
4.1field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

Akira ChinjuKyushu University, Fukuoka, Japan.
Masafumi MoriyamaKyushu University, Fukuoka, Japan.ORCID 0000-0003-2911-2244
Noriko Kakizoe-IshiguroKyushu University, Fukuoka, Japan.
Hu ChenKyushu University, Fukuoka, Japan.
Yuka MiyaharaKyushu University, Fukuoka, Japan.
A S M Rafiul HaqueUdayan Dental College, Rajpara, Bangladesh.
Katsuhiro FurushoNational Center for Geriatrics and Gerontology, Aichi, Japan.
Mizuki SakamotoKyushu University, Fukuoka, Japan.
Kazuki KaiKyushu University, Fukuoka, Japan.
Kotono KibeKyushu University, Fukuoka, Japan and University of Tokyo, Tokyo, Japan.
Sachiko Hatakeyama-FurukawaKyushu University, Fukuoka, Japan.
Miho Ito-OhtaKyushu University, Fukuoka, Japan.
Takashi MaeharaKyushu University, Fukuoka, Japan.
Seiji NakamuraKyushu University, Fukuoka, Japan.
Kyushu University · JPNational Center for Geriatrics and Gerontology · JPPacific Dental College and Hospital · IN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect multiple organs. We previously demonstrated that TLR7-transgenic C57BL/6 mice showed elevated serum IgG1 levels and inflammation with fibrosis in the salivary glands (SGs), lungs, and pancreas. Moreover, we observed extensive Toll-like receptor 7 (TLR-7)-positive CD163+ M2 macrophage infiltration in SGs from IgG4-RD patients. We undertook this study to examine the fibrotic mechanism via the TLR-7 pathway.

methodsGene expression in SGs from human TLR7-transgenic mice and IgG4-RD patients was analyzed using DNA microarrays. We extracted the common up-regulated TLR-7-related genes in SGs from TLR7-transgenic mice and IgG4-RD patients. Finally, we investigated the interaction between CD163+ M2 macrophages and fibroblasts before and after stimulation with the TLR-7 agonist loxoribine.

resultsIn TLR7-transgenic mice and IgG4-RD patients, IRAK3 and IRAK4 were significantly overexpressed. Real-time polymerase chain reaction validated the up-regulation of only IRAK4 in IgG4-RD patients compared with the other groups (P < 0.05). Interleukin-1 receptor-associated kinase 4 (IRAK4) was strongly detected in and around germinal centers in SGs from patients with IgG4-related dacryoadenitis and sialadenitis alone. Double immunofluorescence staining showed that IRAK4-positive cells were mainly colocalized with CD163+ M2 macrophages in SGs (P < 0.05). After stimulation with loxoribine, CD163+ M2 macrophages exhibited significantly enhanced expression of IRAK4 and NF-κB and increased supernatant concentrations of fibrotic cytokines. Finally, we confirmed that the number of fibroblasts was increased by culture with the supernatant of CD163+ M2 macrophages following stimulation with loxoribine (P < 0.05).

conclusionCD163+ M2 macrophages promote fibrosis in IgG4-RD by increasing the production of fibrotic cytokines via TLR-7/IRAK4/NF-κB signaling.

Indexed as

Immunoglobulin G4-Related DiseaseInterleukin-1 Receptor-Associated KinasesNF-kappa BToll-Like Receptor 7AnimalsAntigens, CDAntigens, Differentiation, MyelomonocyticCD163 AntigenCytokinesFibrosisHumansMacrophagesMiceMice, Inbred C57BLMice, TransgenicReceptors, Cell SurfaceAntigens, CDAntigens, Differentiation, MyelomonocyticCD163 AntigenCytokinesInterleukin-1 Receptor-Associated KinasesIRAK4 protein, humanNF-kappa BReceptors, Cell SurfaceToll-Like Receptor 7

Identifiers

PMID34907668
PMCPMC9322461
OpenAlexW4200180998

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.