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Title: Joint NOD2/RIPK2 signaling regulates IL-17 axis and contributes to the development of experimental arthritis
Authors: Manfredo Vieira, Silvio
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
Keywords: Caspase Recruitment Domain Protein 15
Caspase Recruitment Domain Protein 4
Cd4 Antigen
Cxcl1 Chemokine
Receptor Interacting Protein Serine Threonine Kinase 2
Tumor Necrosis Factor
Animals Cell
Animals Experiment
Animals Model
Animals Tissue
Cartilage Degeneration
Controlled Study
Enzyme Activity
Enzyme-linked Immunosorbent Assay
Enzyme Regulation
Immune Response
Priority Journal
Protein Expression
Protein Function
Reverse Transcription Polymerase Chain Reaction
Arthritis, Rheumatoid
Signal Transduction
Arthritis, Experimental
Cells, Cultured
Knee Joint
Mice, Inbred C57bl
Mice, Knockout
Nod1 Signaling Adaptor Protein
Nod2 Signaling Adaptor Protein
Receptor-interacting Protein Serine-threonine Kinases
Serum Albumin, Bovine
Signal Transduction
Issue Date: 2012
metadata.dc.publisher.journal: Journal of Immunology
metadata.dc.relation.ispartof: Volume 188, Número 10, Pags. 5116-5122
Abstract: 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.
metadata.dc.identifier.doi: 10.4049/jimmunol.1004190
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