RESUMO
BACKGROUND: Recent studies show that innate lymphoid cells (ILCs) contribute to the development of chronic inflammation and autoimmune disease. In this study, we assessed the ILC function in the development of rheumatoid arthritis (RA). METHODS: In a mouse model of collagen-induced arthritis (CIA), we identified and purified the ILC subsets in peripheral blood (PB), local lymph nodes (LNs), and joints by fluorescence-activated cell sorting and used quantitative PCR to assess the expression levels of representative cytokines. We also correlated the frequencies of each ILC subset in synovial fluid (SF) with clinical parameters in RA patients. RESULTS: In the CIA model, the proportion of CCR6+ ILC3s to total ILCs in joints with active inflammation significantly increased relative to non-arthritic joints (median 29.6% vs 16.7%, p = 0.035). CCR6+ ILC3s from mice with arthritis expressed significantly higher levels of IL-17A and IL-22 mRNA than did comparable cells from control mice (p < 0.0001 and p = 0.015). In RA patients, the proportion of CCR6+ ILCs in SF was positively correlated with tender joint counts (TJC) and swollen joint counts (SJC) (ρ=0.689, p = 0.0032 and ρ=0.644, p = 0.0071, respectively). Levels of CC chemokine ligand 20 (CCL20) increased in SF of patients with RA and were significantly correlated with CCR6+ ILC number (ρ=0.697, p = 0.0001). CONCLUSION: CCR6+ ILC3s may play some roles in the development of RA through the production of IL-17 and IL-22.
Assuntos
Artrite Reumatoide/imunologia , Regulação da Expressão Gênica , Imunidade Inata , Interleucina-17/biossíntese , Receptores CCR6/genética , Líquido Sinovial/metabolismo , Células Th17/imunologia , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , RNA/genética , Receptores CCR6/biossíntese , Células Th17/metabolismoRESUMO
Aspergillus oryzae has two fructosyl-amino acid oxidase (FAOD) isozymes (AoFao1 and AoFao2), which are different in the substrate specificities. Northern blot analysis showed both FAO genes were induced by autoclave-browned medium containing l-lysine or l-valine. Studies with a mutant, that had a disrupted AoFAO2 gene, revealed that the expression of AoFAO1 by fructosyl l-valine depended on the expression of AoFAO2. Both genes were also induced by one of the FAOD-reaction products, glucosone. In contrast, other alpha-dicarbonyl compounds, which display a similar structure to that of glucosone were not able to induce the genes expression. These results imply that glucosone may contribute to the expression of FAO genes.
