Regulation of neutrophil associated RNASET2 expression in rheumatoid arthritis
Neutrophils (PMNs) are key players of innate immune responses through the release of cytoplasmic granule content and the formation of neutrophil extracellular traps (NETs). RNASET2 is an acidic ribonuclease, recently proposed as an alarmin signal associated with inflammatory responses. Here we show that, along the neutrophil maturation cascade, RNASET2 is expressed in segmented and mature PMNs. In human PMNs, RNASET2 colocalized with primary and tertiary granules and was found to be associated with NETs following PMA or Nigericin stimulation. Similarly, activation of PMNs by soluble immune complexes, a hallmark of several autoimmune diseases, also induced RNASET2-associated NETs. Genome-wide association studies recently identified RNASET2 among a cluster of genes associated with increased susceptibility to develop autoimmune diseases, including rheumatoid arthritis (RA). RNASET2 was found expressed by PMNs and macrophages infiltrating inflamed joints in a murine model of RA (K/BxN Serum-Transfer-Induced Arthritis, STIA), by immunostaining. Similar results were found in synovial biopsies of RA patients with active disease. In addition, we demonstrate that RNASET2 circulating levels correlated with the onset and the severity of disease in two mouse models of inflammatory arthritis, STIA and CIA (Collagen-Induced Arthritis) and in serum of RA patients. These results show that PMNs are an important source of RNASET2 and that its circulating levels are associated with RA development suggesting a role for RNASET2 in the pathogenesis of immune-mediated diseases.
Authors
- Alessia Caproli (ORCID: https://orcid.org/0000-0002-8933-7683)
- Laura Tiberio (ORCID: https://orcid.org/0000-0003-0482-9898)
- Angela Gismondi (ORCID: https://orcid.org/0000-0001-6731-6366)
- Franco Franceschini (ORCID: https://orcid.org/0000-0003-3678-6124)
- Annalisa Del Prete (ORCID: https://orcid.org/0000-0002-3738-412X)
- Tiziana Musso (ORCID: https://orcid.org/0000-0002-7487-6078)
- Sara Scutera (ORCID: https://orcid.org/0000-0002-7431-0875)
- Helena Stabile (ORCID: https://orcid.org/0000-0002-3514-9847)
- Fabrizio Angeli (ORCID: https://orcid.org/0000-0002-5990-2979)
- Francesca Sozio (ORCID: https://orcid.org/0000-0002-9789-1529)
- Silvano Sozzani (ORCID: https://orcid.org/0000-0002-3144-8743)
- William Vermi (ORCID: https://orcid.org/0000-0002-2291-2997)
- Tiziana Schioppa (ORCID: https://orcid.org/0000-0002-6303-6065)
- Valentina Salvi (ORCID: https://orcid.org/0000-0003-4802-1524)
- Laura Andréoli (ORCID: https://orcid.org/0000-0002-9107-3218)
- Daniela Bosisio (ORCID: https://orcid.org/0000-0001-6276-5365)
- Nicola Tamassia (ORCID: https://orcid.org/0000-0003-2990-3003)
- Silvia Piantoni (ORCID: https://orcid.org/0000-0003-0913-0197)
- Mauro Passari (ORCID: https://orcid.org/0000-0002-0502-7865)
- Sonja Vermeren (ORCID: https://orcid.org/0000-0002-8460-0884)
- Francesco Acquati (ORCID: https://orcid.org/0000-0002-9537-400X)
- Mattia Bugatti (ORCID: https://orcid.org/0000-0003-3776-8497)
Institutions
- University of Insubria (IT)
- University of Verona (IT)
- Centre for Inflammation Research (GB)
- Istituto Pasteur (IT)
- IRCCS Humanitas Research Hospital (IT)
- University of Turin (IT)
- University of Brescia (IT)
- Sapienza University of Rome (IT)
- University of Edinburgh (GB)
Publication Details
- Journal
- Scientific Reports
- Published
- 2024-11-05
- DOI
- https://doi.org/10.1038/s41598-024-77694-y
- Citations
- 3
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.72
Funders
- European Commission
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Università degli Studi di Torino
- Università degli Studi di Verona
- Università degli Studi di Brescia
- Ministero dell'Università e della Ricerca