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Macrophage subpopulations in rheumatoid synovium: reduced CD163 expression in CD4+ T lymphocyte-rich
J E Fonseca1, J C W Edwards, S Blades
1University College London, London, UK. mop45465@mail.telepac.pt
Objective:
The cell surface glycoprotein CD163 is a member of the cysteine-rich scavenger receptor family, highly specific for leukocytes of the mononuclear phagocyte lineage. In vitro, it is induced by glucocorticoids, interleukin-6 (IL-6), and IL-10 and down-regulated by interferon-gamma (IFNgamma), indicating that it has a role in antiinflammatory or other immunomodulatory pathways. We assessed CD163 expression in microenvironments within rheumatoid arthritis (RA) synovium to clarify the relationships among CD4+ T lymphocytes, IFNgamma, and macrophage function in RA.
Methods:
Double immunofluorescence and serial immunoenzymatic studies were performed on normal, osteoarthritic, and RA synovium and tonsil with antibodies to CD163, CD45, CD68, CD14, CD3, CD4, CD8, CD19, and IFNgamma.
Results:
CD163 was observed on all CD14+ cells in synovium and tonsil with the exception of cells within larger T lymphocyte clusters in synovium and within tonsillar follicles. All brightly CD14+ cells in or around vessel walls (interpreted as immigrant monocytes) were CD163+. CD163 labeled fewer cells than did CD68 in synovial intima, but all CD45+ intimal cells were CD163+. CD4+,IFNgamma+ T lymphocytes in RA synovium were chiefly localized within clusters containing CD68+, CD163- cells.
Conclusion:
Within RA synovium, CD163 has major advantages as a macrophage marker and does not appear to be restricted to "mature" macrophages. CD163 discriminates between synovial macrophages and synovial intimal fibroblasts, which also stain positively for CD68 in diseased tissue.
Insights
CD163 is a useful marker for identifying macrophages in rheumatoid arthritis (RA) synovium. It helps distinguish macrophages from other cells, offering insights into immune responses in RA.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- CD163 is a scavenger receptor on mononuclear phagocytes, involved in immunomodulatory pathways.
- Its expression is influenced by cytokines like IL-6, IL-10, and IFNgamma, suggesting a role in inflammation.
- Understanding CD163 in rheumatoid arthritis (RA) synovium can clarify macrophage function and T cell interactions.
Purpose of the Study:
- To assess CD163 expression in RA synovium.
- To clarify relationships between CD4+ T lymphocytes, IFNgamma, and macrophage function in RA.
Main Methods:
- Double immunofluorescence and immunoenzymatic studies were performed on synovial and tonsil tissues.
- Antibodies were used to detect CD163, CD45, CD68, CD14, CD3, CD4, CD8, CD19, and IFNgamma.
Main Results:
- CD163 was present on CD14+ cells in synovium and tonsil, excluding T lymphocyte clusters and tonsillar follicles.
- Immigrant monocytes and CD45+ intimal cells expressed CD163.
- CD4+, IFNgamma+ T lymphocytes in RA synovium were found near CD68+, CD163- cells.
Conclusions:
- CD163 is a valuable macrophage marker in RA synovium, not limited to mature macrophages.
- CD163 effectively differentiates synovial macrophages from synovial intimal fibroblasts.
- This marker aids in understanding cellular heterogeneity and function within the RA joint.