Full Papers
Interleukin 9 neutralisation reduces collagen-induced arthritis severity in mouse models
G. Guggino1, M.P. La Manna2, D. Di Liberto3, M. Lo Pizzo4, G. Grasso5, C. Schinocca6, A. Rizzo7, V.L. Lentini8, E. Lo Presti9, M. Shekarkar Azgomi10, F. Dieli11, G. Sireci12, F. Ciccia13
- Department ProMISE, Section of Rheumatology, University of Palermo, Italy. giuliana.guggino@unipa.it
- Department of Biopathology and Medical Biotechnology, University of Palermo, Italy.
- Department of Biopathology and Medical Biotechnology, University of Palermo, Italy.
- Department of Biopathology and Medical Biotechnology, University of Palermo, Italy.
- Department ProMISE, Section of Rheumatology, University of Palermo, Italy.
- Department ProMISE, Section of Rheumatology, University of Palermo, Italy.
- UOC di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
- UOC di Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy.
- Consiglio Nazionale delle Ricerche (CNR), Institute for Biomedical Research and Innovation (IRIB), Palermo, Italy.
- Department of Biopathology and Medical Biotechnology, University of Palermo, Italy.
- Department of Biopathology and Medical Biotechnology, University of Palermo, Italy.
- Department of Biopathology and Medical Biotechnology, University of Palermo, Italy.
- Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples, Italy.
CER15398
2023 Vol.41, N°1
PI 0094, PF 0102
Full Papers
PMID: 35616583 [PubMed]
Received: 07/12/2021
Accepted : 29/03/2022
In Press: 23/05/2022
Published: 23/01/2023
Abstract
OBJECTIVES:
Interleukin 9 (IL-9) is a mediator of tissue damage in several inflammatory diseases. In this study we aimed to evaluate the effects of in vivo IL-9 neutralisation in mice developing collagen induced arthritis (CIA).
METHODS:
DBA/1 were immunised with collagen in Freund’s complete adjuvant (CFA) to induce arthritis. Anti-IL-9 mAb was injected in mice after the onset of arthritis (Group A) or on the same day as sensitisation and again on the day of the challenge (Group B). Histological analysis was performed in joints of mice and spleen cells were also analysed by flow cytometry. A geneset analysis was carried out on whole tarsal joint tissue transcriptomes.
RESULTS:
IL-9 was over-expressed in swollen joints of mice developing arthritis. Treatment with anti-IL-9 mAb after arthritis onset efficiently down-modulated the severity of joint inflammation. Similarly, anti-IL-9 mAb administered on the same day as sensitisation and on the day of challenge also delayed the onset of arthritis. Anti-IL-9 mAb injection after the onset of arthritis was associated with a decrease of CD4+ TNF-α+ cells and an increase of CD4+ FoxP3+ IL-10+ cells. Geneset analysis in CIA showed an up-regulation of GATA3 with no significant direct interactions between IL-9 and GATA3, which instead was mediated by IL-5 through STAT6.
CONCLUSIONS:
Our results suggest that IL-9 is involved in the immunopathogenesis of CIA. Further implications for the clinical translation of our findings are discussed.
