Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model

Ringer M, Maccataio A, Zapf R, Gaculenko A, Adam S, Aust O, Aust O, Loskarn S, Luther J, Aksoy B, Popp V, Weidner D, Eck M, Munoz LE, Bozec A, Uderhardt S, Bäuerle T, Schett G, Krönke G, Hüffmeier U, Frey S, Steffen U (2025)

Publication Language: English

Publication Type: Journal article

Publication year: 2025

Journal

Journal of Leukocyte Biology Society for Leukocyte Biology

Book Volume: 117

Article Number: qiaf110

Journal Issue: 9

DOI: 10.1093/jleuko/qiaf110

Abstract

Psoriasis is a systemic inflammatory skin disorder with a prevalence of 2% in adults. Up to 30% of affected individuals further develop psoriatic arthritis (PsA), which is characterized by additional joint inflammation. Myeloperoxidase (MPO) is strongly expressed by neutrophils and, to a lesser extent, also by other myeloid cells. MPO converts hydrogen peroxide to secondary reactive oxygen species (ROS) and is thus primarily considered to induce tissue damage. However, recent studies suggest a protective role of MPO in psoriatic diseases. We aimed to investigate the role of MPO in PsA using the mouse model of mannan-induced PsA. MPO-deficient (Mpo-/-) mice showed exacerbated skin inflammation, joint swelling, and bone degradation associated with increased infiltration of neutrophils, classically activated macrophages, and T cells as well as increased inflammatory cytokine expression in the affected tissues. In the absence or blockade of MPO, in vitro neutrophil stimulation resulted in reduced NET formation and enhanced degranulation characterized by increased neutrophil elastase (NE) activity. In addition, in vitro differentiated macrophages from Mpo-/- mice showed increased interleukin (Il)-6 mRNA expression. Altogether, our findings suggest that MPO controls inflammatory responses in PsA, at least in part, by reducing neutrophil degranulation and serine protease release and, putatively, by reducing inflammatory cytokine production by macrophages.

Authors with CRIS profile

Mark Ringer Department of Medicine 3 – Rheumatology and Immunology Antonio Maccataio Department of Medicine 3 – Rheumatology and Immunology Rico Zapf Department of Medicine 3 – Rheumatology and Immunology Anastasia Gaculenko Department of Medicine 3 – Rheumatology and Immunology Susanne Adam Department of Medicine 3 – Rheumatology and Immunology Oliver Aust Department of Medicine 3 – Rheumatology and Immunology Burak Aksoy Institute of Clinical and Molecular Virology Vanessa Popp Institute of Radiology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Aline Bozec Professur für Experimentelle Immuntherapie Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology Tobias Bäuerle Professur für Multimodale Bildgebung in der präklinischen Forschung Georg Schett Lehrstuhl für Innere Medizin III Gerhard Krönke Department of Medicine 3 – Rheumatology and Immunology Ulrike Hüffmeier Institute of Human Genetics Silke Frey Department of Medicine 3 – Rheumatology and Immunology Ulrike Steffen Department of Medicine 3 – Rheumatology and Immunology

How to cite

APA:

Ringer, M., Maccataio, A., Zapf, R., Gaculenko, A., Adam, S., Aust, O.,... Steffen, U. (2025). Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model. Journal of Leukocyte Biology, 117(9). https://doi.org/10.1093/jleuko/qiaf110

MLA:

Ringer, Mark, et al. "Loss of myeloperoxidase aggravates skin and joint inflammation in the mannan-induced psoriatic arthritis mouse model." Journal of Leukocyte Biology 117.9 (2025).

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