Expansion of a unique macrophage subset in rheumatoid arthritis synovial lining layer

M Tanaka1, T Nagai, Y Tsuneyoshi

  • 1Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Insights

Z39Ig+ cells, identified as macrophages, are found in synovium. Their expansion, particularly Z39Ig+CD11c+ cells, is characteristic of rheumatoid arthritis (RA) synovial lining, distinguishing it from osteoarthritis and psoriatic arthritis.

Area of Science:

  • Immunology
  • Pathology
  • Cell Biology

Background:

  • The Z39Ig protein functions as a complement receptor for C3b and iC3b.
  • This protein is expressed on resident tissue macrophages across various organs.
  • Understanding macrophage distribution in synovium is crucial for inflammatory arthritis research.

Purpose of the Study:

  • To investigate the distribution and characteristics of Z39Ig+ cells in synovial tissue.
  • To compare Z39Ig+ cell populations in rheumatoid arthritis (RA), osteoarthritis (OA), and psoriatic arthritis (PsA) synovium.
  • To identify specific macrophage subsets within the RA synovium.

Main Methods:

  • Production of a monoclonal anti-Z39Ig antibody.
  • Double immunostaining of synovial tissues (normal, RA, OA, PsA) with antibodies against Z39Ig, macrophages, fibroblast-like synoviocytes, complement receptors, and dendritic cells.
  • Isolation and analysis of Z39Ig+CD11c+ and Z39Ig+CD11c- cells from RA synovium using cell sorting and electron microscopy.

Main Results:

  • Z39Ig protein expression was consistently observed on intimal macrophages in all examined synovium types.
  • The synovial lining layer in RA showed increased numbers and ratios of Z39Ig+CD11c+ cells compared to OA and PsA.
  • Ultrastructural analysis confirmed Z39Ig+CD11c+ cells as macrophages with features like secondary lysosomes and swollen mitochondria.
  • Expansion of Z39Ig+CD11c+ cells was a distinct characteristic of the RA synovial lining.

Conclusions:

  • Z39Ig+ cells serve as reliable markers for resident tissue macrophages in normal synovium.
  • These cells are also indicative of macrophages within the synovial lining layer of inflammatory arthritis.
  • The expansion of Z39Ig+CD11c+ cells is a specific feature of the RA synovial lining layer, differentiating it from other arthritic conditions.