Joint NOD2/RIPK2 signaling regulates IL-17 axis and contributes to the development of experimental arthritis

• Autor(a) principal: Manfredo Vieira, Silvio
• Data de Publicação: 2012
• Outros Autores: Cunha, Thiago Mattar, França, Rafael Freitas de Oliveira, Pinto, Larissa Garcia, Talbot, Jhimmy, Turato, Walter Miguel, Lemos, Henrique Paula, Lima, Jonilson Berlink, Verri, Waldiceu A., Almeida, Sërgio C.L., Ferreira, Seérgio Henrique, Louzada-Jünior, Paulo, Zamboni, Darío Simões, Cunha, Fernando Queiroz
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional do INPA
• Texto Completo: https://repositorio.inpa.gov.br/handle/1/16128
• topic: Caspase Recruitment Domain Protein 15; Caspase Recruitment Domain Protein 4; Cd4 Antigen; Cxcl1 Chemokine; Interleukin-17; Interleukin-1beta; Interleukin-23; Interleukin-6; Proteoglycan; Receptor Interacting Protein Serine Threonine Kinase 2; Tumor Necrosis Factor; Animals Cell; Animals Experiment; Animals Model; Animals Tissue; Arthritis; Cartilage Degeneration; Controlled Study; Enzyme Activity; Enzyme-linked Immunosorbent Assay; Enzyme Regulation; Histopathology; Immune Response; Mouse; Neutrophil; Nociception; Nonhuman; Priority Journal; Protein Expression; Protein Function; Reverse Transcription Polymerase Chain Reaction; Arthritis, Rheumatoid; Signal Transduction; Synovium; Animal; Arthritis, Experimental; Cattle; Cells, Cultured; Interleukin-17; Knee Joint; Mice; Mice, Inbred C57bl; Mice, Knockout; Nod1 Signaling Adaptor Protein; Nod2 Signaling Adaptor Protein; Receptor-interacting Protein Serine-threonine Kinases; Serum Albumin, Bovine; Signal Transduction

Intracellular pattern recognition receptors such as the nucleotide-binding oligomerization domain (NOD)-like receptors family members are key for innate immune recognition of microbial infection and may play important roles in the development of inflammatory diseases, including rheumatic diseases. In this study, we evaluated the role of NOD1 and NOD2 on development of experimental arthritis. Ag-induced arthritis was generated in wild-type, NOD1 -/-, NOD2 -/-, or receptor-interacting serine-threonine kinase 2 -/- (RIPK2 -/-) immunized mice challenged intra-articularly with methylated BSA. Nociception was determined by electronic Von Frey test. Neutrophil recruitment and histopathological analysis of proteoglycan lost was evaluated in inflamed joints. Joint levels of inflammatory cytokine/chemokine were measured by ELISA. Cytokine (IL-6 and IL-23) and NOD2 expressions were determined in mice synovial tissue by RT-PCR. The NOD2 -/- and RIPK2 -/-, but not NOD1 -/-, mice are protected from Ag-induced arthritis, which was characterized by a reduction in neutrophil recruitment, nociception, and cartilage degradation. NOD2/RIPK2 signaling impairment was associated with a reduction in proinflammatory cytokines and chemokines (TNF, IL-1b, and CXCL1/KC). IL-17 and IL-17 triggering cytokines (IL-6 and IL-23) were also reduced in the joint, but there is no difference in the percentage of CD4 + IL-17 + cells in the lymph node between arthritic wild-type and NOD2 -/- mice. Altogether, these findings point to a pivotal role of the NOD2/RIPK2 signaling in the onset of experimental arthritis by triggering an IL-17-dependent joint immune response. Therefore, we could propose that NOD2 signaling is a target for the development of new therapies for the control of rheumatoid arthritis. Copyright © 2012 by The American Association of Immunologists, Inc.