Regulation of neutrophil associated RNASET2 expression in rheumatoid arthritis.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Arthritis, Rheumatoid*/genetics ; Arthritis, Rheumatoid*/metabolism ; Arthritis, Rheumatoid*/pathology ; Neutrophils*/metabolism ; Extracellular Traps*/metabolism; Humans ; Animals ; Mice ; Male ; Ribonucleases/metabolism ; Ribonucleases/genetics ; Female ; Arthritis, Experimental/genetics ; Arthritis, Experimental/metabolism ; Arthritis, Experimental/pathology ; Macrophages/metabolism ; Disease Models, Animal ; Gene Expression Regulation ; Tumor Suppressor Proteins

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.
(© 2024. The Author(s).)

Erratum in: Sci Rep. 2024 Nov 19;14(1):28610. doi: 10.1038/s41598-024-79660-0. (PMID: 39562651)

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PRIN2017 No. NTK4HY Ministero dell'Università e della Ricerca; PRIN2017 No. NTK4HY Ministero dell'Università e della Ricerca; PNRR-European Union PE08 Age-It Ministero dell'Università e della Ricerca; PRIN2017 No. NTK4HY Ministero dell'Università e della Ricerca; PRIN2017 No. NTK4HY Ministero dell'Università e della Ricerca

EC 3.1.27.- (RNASET2 protein, human)
EC 3.1.- (Ribonucleases)
0 (Tumor Suppressor Proteins)

Date Created: 20241105 Date Completed: 20241105 Latest Revision: 20241120

20241120

PMC11538310

10.1038/s41598-024-77694-y

39500942