Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis - PubMed (original) (raw)
. 2007 Aug;56(8):2492-502.
doi: 10.1002/art.22748.
Affiliations
- PMID: 17665400
- DOI: 10.1002/art.22748
Free article
Inflammation and ectopic lymphoid structures in rheumatoid arthritis synovial tissues dissected by genomics technology: identification of the interleukin-7 signaling pathway in tissues with lymphoid neogenesis
Trieneke C G Timmer et al. Arthritis Rheum. 2007 Aug.
Free article
Abstract
Objective: In approximately 25% of synovial tissues from rheumatoid arthritis (RA) patients, infiltrates of T cells, B cells, and follicular dendritic cells (FDCs) are spatially organized into structures resembling lymph nodes with germinal centers. The remainder of the tissues lack FDCs and show either a diffuse or an aggregated T cell and B cell infiltrate. To gain more insight into this specific disease process, we sought to identify the genes expressed in RA tissues with ectopic lymphoid structures.
Methods: Gene expression profiling of RA synovial tissues was determined by complementary DNA microarray analysis and quantitative real-time polymerase chain reaction. The presence of lymphoid follicles and localization of interleukin-7 (IL-7) in synovial tissue sections was determined by immunofluorescence staining using specific antibodies.
Results: Findings of gene expression analysis confirmed previous reports that tissues with lymphoid structures showed elevated expression of CXCL13, CCL21, CCR7, and lymphotoxin alpha and beta messenger RNA. In addition, the tissues also showed enhanced expression of the chemokines CXCL12 and CCL19 and the associated receptors CXCR4 and CXCR5, which are important for the attraction of T cells, B cells, and dendritic cells. Pathway analysis revealed increased expression of genes involved in JAK/STAT signaling, T cell- and B cell-specific pathways, Fcepsilon receptor type I signaling in mast cells, and IL-7 signal transduction in the tissues with ectopic lymphoid follicles, accompanied by increased expression of IL-7 receptor alpha (IL-7Ralpha)/IL-2Rgamma chains and IL-7. Protein expression of IL-7 in RA tissues was localized within fibroblast-like synoviocytes, macrophages, and blood vessels and was colocalized with extracellular matrix structures around the B cell follicles.
Conclusion: Activation of the IL-7 pathway may play an important role in lymphoid neogenesis, analogous to its role in the development of normal lymphoid tissue.
Similar articles
- Elevated expression of interleukin-7 receptor in inflamed joints mediates interleukin-7-induced immune activation in rheumatoid arthritis.
Hartgring SA, van Roon JA, Wenting-van Wijk M, Jacobs KM, Jahangier ZN, Willis CR, Bijlsma JW, Lafeber FP. Hartgring SA, et al. Arthritis Rheum. 2009 Sep;60(9):2595-605. doi: 10.1002/art.24754. Arthritis Rheum. 2009. PMID: 19714586 - Synovial lymphoid neogenesis does not define a specific clinical rheumatoid arthritis phenotype.
Thurlings RM, Wijbrandts CA, Mebius RE, Cantaert T, Dinant HJ, van der Pouw-Kraan TC, Verweij CL, Baeten D, Tak PP. Thurlings RM, et al. Arthritis Rheum. 2008 Jun;58(6):1582-9. doi: 10.1002/art.23505. Arthritis Rheum. 2008. PMID: 18512774 - Regulation of pre-B cell colony-enhancing factor by STAT-3-dependent interleukin-6 trans-signaling: implications in the pathogenesis of rheumatoid arthritis.
Nowell MA, Richards PJ, Fielding CA, Ognjanovic S, Topley N, Williams AS, Bryant-Greenwood G, Jones SA. Nowell MA, et al. Arthritis Rheum. 2006 Jul;54(7):2084-95. doi: 10.1002/art.21942. Arthritis Rheum. 2006. PMID: 16802343 - Morphological and molecular pathology of the B cell response in synovitis of rheumatoid arthritis.
Magalhães R, Stiehl P, Morawietz L, Berek C, Krenn V. Magalhães R, et al. Virchows Arch. 2002 Nov;441(5):415-27. doi: 10.1007/s00428-002-0702-1. Epub 2002 Nov 5. Virchows Arch. 2002. PMID: 12447670 Review. - Chemokine-mediated control of T cell traffic in lymphoid and peripheral tissues.
Ebert LM, Schaerli P, Moser B. Ebert LM, et al. Mol Immunol. 2005 May;42(7):799-809. doi: 10.1016/j.molimm.2004.06.040. Epub 2004 Nov 23. Mol Immunol. 2005. PMID: 15829268 Review.
Cited by
- Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts.
Okamoto K, Araki Y, Aizaki Y, Tanaka S, Kadono Y, Mimura T. Okamoto K, et al. Sci Rep. 2024 May 9;14(1):10610. doi: 10.1038/s41598-024-60860-7. Sci Rep. 2024. PMID: 38719857 Free PMC article. - Meningeal inflammation as a driver of cortical grey matter pathology and clinical progression in multiple sclerosis.
Magliozzi R, Howell OW, Calabrese M, Reynolds R. Magliozzi R, et al. Nat Rev Neurol. 2023 Aug;19(8):461-476. doi: 10.1038/s41582-023-00838-7. Epub 2023 Jul 3. Nat Rev Neurol. 2023. PMID: 37400550 Review. - Editorial: Autoantibodies and the role of RNA/RNA therapy in rheumatoid arthritis.
Ma K. Ma K. Front Immunol. 2022 Oct 20;13:1037843. doi: 10.3389/fimmu.2022.1037843. eCollection 2022. Front Immunol. 2022. PMID: 36341462 Free PMC article. No abstract available. - Two Main Cellular Components in Rheumatoid Arthritis: Communication Between T Cells and Fibroblast-Like Synoviocytes in the Joint Synovium.
Tu J, Huang W, Zhang W, Mei J, Zhu C. Tu J, et al. Front Immunol. 2022 Jul 1;13:922111. doi: 10.3389/fimmu.2022.922111. eCollection 2022. Front Immunol. 2022. PMID: 35844494 Free PMC article. Review. - Significance of IL-7 and IL-7R in RA and autoimmunity.
Meyer A, Parmar PJ, Shahrara S. Meyer A, et al. Autoimmun Rev. 2022 Jul;21(7):103120. doi: 10.1016/j.autrev.2022.103120. Epub 2022 May 17. Autoimmun Rev. 2022. PMID: 35595051 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical