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The mode of action of IL-23 in experimental inflammatory arthritic pain and disease
- Source :
- Arthritis Research & Therapy, Vol 26, Iss 1, Pp 1-13 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Objectives We have previously reported using gene-deficient mice that the interleukin (IL)-23p19 subunit is required for the development of innate immune-driven arthritic pain and disease. We aimed to explore here, using a number of in vivo approaches, how the IL-23p19 subunit can mechanistically control arthritic pain and disease in a T- and B- lymphocyte-independent manner. Methods We used the zymosan-induced arthritis (ZIA) model in wild-type and Il23p19 −/− mice, by a radiation chimera approach, and by single cell RNAseq and qPCR analyses, to identify the IL23p19-expressing and IL-23-responding cell type(s) in the inflamed joints. This model was also utilized to investigate the efficacy of IL-23p19 subunit blockade with a neutralizing monoclonal antibody (mAb). A novel IL-23-driven arthritis model was established, allowing the identification of putative downstream mediators of IL-23 in the control of pain and disease. Pain and arthritis were assessed by relative static weight distribution and histology, respectively. Results We present evidence that (i) IL-23p19+ non-bone marrow-derived macrophages are required for the development of ZIA pain and disease, (ii) prophylactic and therapeutic blockade of the IL-23p19 subunit ameliorate ZIA pain and disease and (iii) systemically administered IL-23 can induce arthritic pain and disease in a manner dependent on TNF, GM-CSF, CCL17 and cyclooxygenase activity, but independently of lymphocytes, CGRP, NGF and substance P. Conclusions The data presented should aid IL-23 targeting both in the choice of inflammatory disease to be treated and the design of clinical trials.
Details
- Language :
- English
- ISSN :
- 14786362
- Volume :
- 26
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Arthritis Research & Therapy
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.888be7f191d14f12b7b922d2269b3be3
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13075-024-03380-z