Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Joint production of IL-22 participates in the initial phase of antigen-induced arthritis through IL-1 beta production

Full text
Author(s):
Pinto, Larissa G. [1] ; Talbot, Jhimmy [1] ; Peres, Raphael S. [1] ; Franca, Rafael F. [1] ; Ferreira, Sergio H. [1] ; Ryffel, Bernhard [2, 3] ; Aves-Filho, Jose Carlos F. [1] ; Figueiredo, Florencio [4] ; Cunha, Thiago M. [1] ; Cunha, Fernando Q. [1]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, BR-14049900 Sao Paulo - Brazil
[2] Univ Orleans, F-45071 Orleans - France
[3] CNRS, UMR Mol & Expt Immunol & Neurogenet 7355, F-45071 Orleans - France
[4] Univ Brasilia, Sch Med, Lab Pathol, BR-70910900 Brasilia, DF - Brazil
Total Affiliations: 4
Document type: Journal article
Source: ARTHRITIS RESEARCH & THERAPY; v. 17, SEP 2 2015.
Web of Science Citations: 15
Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by neutrophil articular infiltration, joint pain and the progressive destruction of cartilage and bone. IL-22 is a key effector molecule that plays a critical role in autoimmune diseases. However, the function of IL-22 in the pathogenesis of RA remains controversial. In this study, we investigated the role of IL-22 in the early phase of antigen-induced arthritis (AIA) in mice. Methods: AIA was induced in C57BL/6, IL-22(-/-), ASC(-/-) and IL-1R1(-/-) immunized mice challenged intra-articularly with methylated bovine serum albumin (mBSA). Expression of IL-22 in synovial membranes was determined by RT-PCR. Articular hypernociception was evaluated using an electronic von Frey. Neutrophil recruitment and histopathological analyses were assessed in inflamed knee joint. Joint levels of inflammatory mediators and mBSA-specific IgG concentration in the serum were measured by ELISA. Results: The IL-22 mRNA expression and protein levels in synovial tissue were increased during the onset of AIA. In addition, pharmacological inhibition (anti-IL-22 antibody) and genetic deficiency (IL-22(-/-) mice) reduced articular pain and neutrophil migration in arthritic mice. Consistent with these findings, recombinant IL-22 joint administration promoted articular inflammation per se in WT mice, restoring joint nociception and neutrophil infiltration in IL-22(-/-) mice. Moreover, IL-22-deficient mice showed reduced synovitis (inflammatory cell influx) and lower joint IL-1 alpha levels, whereas the production of IL-17, MCP-1/CCL2, and KC/CXCL1 and the humoral immune response were similar, compared with WT mice. Corroborating these results, the exogenous administration of IL-22 into the joints induced IL-1 alpha production in WT mice and reestablished IL-1 beta production in IL-22(-/-) mice challenged with mBSA. Additionally, IL-1R1(-/-) mice showed attenuated inflammatory features induced by mBSA or IL-22 challenge. Articular nociception and neutrophil migration induced by IL-22 were also reduced in ASC(-/-) mice. Conclusions: These results suggest that IL-22 plays a pro-inflammatory/pathogenic role in the onset of AIA through an ASC-dependent stimulation of IL-1 beta production. (AU)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support type: Research Projects - Thematic Grants