RNA-seq characterization of histamine-releasing mast cells as potential therapeutic target of osteoarthritis
Copyright © 2022. Published by Elsevier Inc.
| Publié dans: | Clinical immunology (Orlando, Fla.). - 1999. - 244(2022) vom: 15. Nov., Seite 109117 |
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| Auteur principal: | |
| Autres auteurs: | , , , , , , , , , , , , , , |
| Format: | Article en ligne |
| Langue: | English |
| Publié: |
2022
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| Accès à la collection: | Clinical immunology (Orlando, Fla.) |
| Sujets: | Journal Article Research Support, U.S. Gov't, Non-P.H.S. Histamine Histamine H(1) receptor (H(1)R) Mast cell Osteoarthritis RNA-Seq Il1rl1 protein, mouse Interleukin-1 Receptor-Like 1 Protein Receptors, Histamine H1 plus... |
| Résumé: | Copyright © 2022. Published by Elsevier Inc. OBJECTIVE: Mast cells in the osteoarthritis (OA) synovium correlate with disease severity. This study aimed to further elucidate the role of mast cells in OA by RNA-Seq analysis and pharmacological blockade of the activity of histamine, a key mast cell mediator, in murine OA METHODS: We examined OA synovial tissues and fluids by flow cytometry, immunostaining, single-cell and bulk RNA-Seq, qPCR, and ELISA. Cetirizine, a histamine H1 receptor (H1R) antagonist, was used to treat the destabilization of the medial meniscus (DMM) mouse model of OA RESULTS: Flow cytometry and immunohistology analysis of OA synovial cells revealed KIT+ FcεRI+ and TPSAB1+ mast cells. Single-cell RNA-Seq of OA synovial cells identified the expression of prototypical mast cell markers KIT, TPSAB1, CPA3 and HDC, as well as distinctive markers HPGD, CAVIN2, IL1RL1, PRG2, and CKLF, confirmed by bulk RNA-Seq and qPCR. A mast cell prototypical marker expression score classified 40 OA patients into three synovial pathotypes: mast cell-high, -medium, and -low. Additionally, we detected mast cell mediators including histamine, tryptase AB1, CPA3, PRG2, CAVIN2, and CKLF in OA synovial fluids. Elevated H1R expression was detected in human OA synovium, and treatment of mice with the H1 receptor antagonist cetirizine reduced the severity and OA-related mediators in DMM CONCLUSION: Based on differential expression of prototypical and distinct mast cell markers, human OA joints can be stratified into mast cell-high, -medium, and -low synovial tissue pathotypes. Pharmacologic blockade of histamine activity holds the potential to improve OA disease outcome |
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| Description: | Date Completed 12.10.2022 Date Revised 29.12.2023 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1521-7035 |
| DOI: | 10.1016/j.clim.2022.109117 |