Crosstalk between macrophages and fibroblasts contributes to inflammation and damage in giant cell arteritis.
Objectives Giant cell arteritis (GCA) is a large vessel vasculitis characterized by arterial wall inflammation and remodelling. Macrophages and fibroblasts are abundantly present in arteries affected by GCA, but their crosstalk in GCA pathogenesis is largely unknown. Here we investigated the interac...
| Publicado en: | Rheumatology Vol. 65; no. 3; pp. 1 - 12 |
|---|---|
| Autores principales: | , , , , , , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Oxford University Press / USA
Mar2026
|
| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=192667732&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 192667732 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 14620324 DN9 jtl: Rheumatology issn: 14620324 maglogo: N pubinfo: dt: Mar2026 vid: 65 iid: 3 pid: 622 pub: Oxford University Press / USA artinfo: ui: 192667732 192667732 192667732 10.1093/rheumatology/keaf408 192667732 ppf: 1 ppct: 11 formats: tig: atl: Crosstalk between macrophages and fibroblasts contributes to inflammation and damage in giant cell arteritis. aug: au: Xu, Shuang Jiemy, William F Zhang, Anqi Walinga, Fokke Nijenhuis, Miranda Hensema, Elien Abdulahad, Wayel Geest, Kornelis SM van der Heeringa, Peter Boots, Annemieke affil: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands sug: subj: Giant Cell Arteritis Pathology Macrophages Pathology Fibroblasts Pathology Inflammation Physiopathology Giant Cell Arteritis Diagnosis Biological Markers Diagnostic Use Human Male Female Adult Middle Age Aged Aged, 80 and Over Prospective Studies Nonexperimental Studies Vasculitis Pathology Arteries Pathology Extracellular Matrix Metabolism Cell Communication Signal Transduction Colony-Stimulating Factors Metabolism Interleukins Matrix Metalloproteinases Proteins Monocytes Immunohistochemistry Cell Culture Techniques Polymerase Chain Reaction Enzyme-Linked Immunosorbent Assay In Vitro Studies Genes Disease Progression Descriptive Statistics Data Analysis Software Mann-Whitney U Test Spearman's Rank Correlation Coefficient Friedman Test Wilcoxon Rank Sum Test ROC Curve Logistic Regression Cytokines Correlational Studies Chemokines Funding Source Adult: 19-44 years Middle Aged: 45-64 years Aged: 65+ years Aged, 80 & over Male Female ab: Objectives Giant cell arteritis (GCA) is a large vessel vasculitis characterized by arterial wall inflammation and remodelling. Macrophages and fibroblasts are abundantly present in arteries affected by GCA, but their crosstalk in GCA pathogenesis is largely unknown. Here we investigated the interaction between macrophages and fibroblasts in GCA-affected arteries and in vitro. Methods Immunostaining was performed to detect macrophages (CD68, CD206, FRβ), fibroblasts (CD90, CD200), GM-CSF, M-CSF, IL-6, MMP-3 and tenascin-C in GCA-positive temporal arteries (n = 9) and aorta tissues (n = 9). Serum tenascin-C levels were measured by ELISA in GCA patients (n = 36) and healthy controls (n = 46). In vitro , monocytes isolated from peripheral blood mononuclear cells of healthy donors (n = 10) were incubated with GM-CSF or M-CSF for 8 days to induce macrophage differentiation. GM-CSF/M-CSF-macrophage-conditioned medium (MCM) was added to human aortic adventitial fibroblast (HAoAF) cultures for 24 h. mRNA expression of proinflammatory cytokines(IL-6, IL-1β), growth factors (GM-CSF, M-CSF), matrix metalloproteinase (MMP-1, MMP-3), chemokines (CCL2, CX3CL1), extracellular matrix proteins (Col1a1, Col1a2, Col3a1, fibronectin-1, tenascin-C) and phenotypic markers (fibroblast activation protein [FAP], podoplanin [PDPN], α-smooth muscle actin, CD200) in cultured fibroblasts were examined by qPCR. Results In GCA-affected arteries, pro-inflammatory CD90+IL-6+ fibroblasts, but not pro-resolving CD90+CD200+ fibroblasts, were spatially associated with macrophages. Adventitial CD90+ fibroblasts expressed GM-CSF and/or M-CSF, which linked to macrophage subset distribution. In vitro , both GM-CSF- and, to a lesser extent, M-CSF-derived MCM upregulated mRNA expression of IL-6, GM-CSF, M-CSF, CCL2, PDPN and CD200 in fibroblasts. Upregulation of IL-1β, MMP-3, Col3a1 and tenascin-C and downregulation of FAP in fibroblasts was observed with GM-CSF-derived MCM. Adventitial CD90+ fibroblasts in GCA-affected temporal arteries also expressed MMP-3 and tenascin-C. Serum levels of tenascin-C in patients with treatment-naïve GCA were significantly higher than those in healthy controls, showing a good diagnostic accuracy (area under the curve 0.89). Conclusion The interaction between fibroblasts and macrophages may contribute to the chronicity and progression of GCA and deserves further investigation. Serum tenascin-C is a candidate biomarker for GCA diagnosis. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|