- Titel
- Transferrin receptor 2 deficiency promotes macrophage polarization and inflammatory arthritis
- Zitierfähige Url:
- https://nbn-resolving.org/urn:nbn:de:bsz:14-qucosa2-966408
- Quellenangabe
- Redox Biology
Erscheinungsjahr: 2023
Jahrgang: 60
E-ISSN: 2213-2317
Artikelnummer: 102616 - Erstveröffentlichung
- 2023
- Abstract (EN)
- Objective: Rheumatoid arthritis is an inflammatory joint disease in which synovial iron deposition has been described. Transferrin receptor 2 (Tfr2) represents a critical regulator of systemic iron levels. Loss of Tfr2 function in humans and mice results in iron overload. As iron contributes to inflammatory processes, we investigated whether Tfr2-deletion affects the pathogenesis of inflammatory arthritis in an iron-dependent manner. - Methods: Using a global and conditional genetic disruption of Tfr2, we assessed the relevance of Tfr2 in K/BxN serum-transfer arthritis (STA) and macrophage polarization. - Results: Male Tfr2⁻⸍⁻ mice subjected to STA developed pronounced joint swelling, and bone erosion as compared to Tfr2⁺⸍⁺ littermate-controls (P < 0.01). Furthermore, an increase of neutrophils and macrophages/monocytes was observed in the inflammatory infiltrate within the paws of Tfr2⁻⸍⁻ mice. To elucidate whether Tfr2 in myeloid cells has a direct role in the pathogenesis of arthritis or whether the effects were mediated via the systemic iron overload, we induced STA in Tfr2ᶠˡ⸍ᶠˡ-LysMCre + mice, which showed normal iron-loading. Cre + female mice displayed increased disease development compared to Cre-controls. As macrophages regulate iron availability and innate immunity, we hypothesized that Tfr2-deficiency would polarize macrophages toward a pro-inflammatory state (M1) that contributes to arthritis progression. In response to IFN-γ stimulation, Tfr2⁻⸍⁻ macrophages showed increased expression of M1-like cytokines, IFN-γ-target genes, nitric-oxide production, and prolonged STAT1 activation compared to Tfr2⁺⸍⁺ macrophages (P < 0.01), while pre-treatment with ruxolitinib abolished Tfr2-driven M1-like polarization. - Conclusion: Taken together, these findings suggest a protective role of Tfr2 in macrophages on the progression of arthritis via suppression of M1-like polarization.
- Andere Ausgabe
- Link zum Artikel, der zuerst in der Zeitschrift „Redox Biology” im Verlag Elsevier erschienen ist.
DOI: 10.1016/j.redox.2023.102616 - Verweis
- Ergänzendes Material ist unter folgendem Link zu finden.
Link: https://www.sciencedirect.com/science/article/pii/S2213231723000174?via%3Dihub#appsec1 - Freie Schlagwörter (EN)
- Transferrin receptor 2 deficiency, Transferrin receptor 2 (Tfr2), macrophage polarization, Rheumatoid arthritis, Tfr2-deletion
- Klassifikation (DDC)
- 570
- Verlag
- Elsevier, Amsterdam [u.a.]
- Version / Begutachtungsstatus
- publizierte Version / Verlagsversion
- URN Qucosa
- urn:nbn:de:bsz:14-qucosa2-966408
- Veröffentlichungsdatum Qucosa
- 05.11.2025
- Dokumenttyp
- Artikel
- Sprache des Dokumentes
- Englisch
- Lizenz / Rechtehinweis
CC BY-NC-ND 4.0