Title:	Joint production of IL-22 participates in the initial phase of antigen-induced arthritis through IL-1β production
Authors:	Pinto, Larissa G. Talbot, Jhimmy Peres, Raphael S. Franca, Rafael F. Ferreira, Sérgio Henrique Ryffel, Bernhard Alves-Filho, José Carlos F. Cavalcanti Neto, Florêncio Figueiredo Cunha, Thiago Mattar Cunha, Fernando de Queiroz
Assunto::	Ratos Imunização Neutrófilos Artrite reumatoide
Issue Date:	2015
Publisher:	BioMed Central
Citation:	PINTO, Larissa G. et al. Joint production of IL-22 participates in the initial phase of antigen-induced arthritis through IL-1β production. Arthritis Research & Therapy , v. 17, 235, 2015. DOI: https://doi.org/10.1186/s13075-015-0759-2. Disponível em: https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-015-0759-2. Acesso em: 17 maio 2021.
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-1β 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-1β production in WT mice and reestablished IL-1β 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-1β production.
metadata.dc.description.unidade:	Faculdade de Medicina (FMD)
Licença::	(CC BY) - © 2015 Pinto et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
DOI:	https://doi.org/10.1186/s13075-015-0759-2
Appears in Collections:	Artigos publicados em periódicos e afins

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