Joint-tissue signals strengthen inflammation-limiting cells in mice
A peer-reviewed study finds that immune cells gain inflammation-limiting functions through signals from joint tissue. In arthritic mice, stimulating the CD200 receptor reduced inflammation and supported a suppressive cell subgroup. Human samples showed related associations, but the mechanism was tested through animal and cell experiments. The results distinguish a cell’s abundance in blood from its function inside affected tissue.
Science··Morning
Suppressive function develops inside joint tissue
Immune cells taken from inflamed mouse joints suppressed T-cell proliferation, while similar cells circulating in blood did not show the same function. The peer-reviewed arthritis study investigated granulocytic myeloid-derived suppressor cells, a group that can restrain immune responses. Human blood and tissue observations guided experiments in mice and cell cultures. In people with axial spondyloarthritis, an inflammatory disease affecting the spine and nearby joints, more circulating cells accompanied greater disease activity rather than better inflammation control.[1]
CD200 signalling supports a functional subgroup
Fibroblasts, cells forming part of the joint’s supporting tissue, were identified as a source of CD200 signals to immune-cell precursors. Stimulating the CD200R1 receptor with an antibody was followed by less arthritis in mice and a greater share of suppressor cells carrying PD-L1, a protein involved in immune regulation. Total suppressor-cell numbers did not expand correspondingly. Blocking CD200 had the opposite effect, reducing that subgroup and worsening inflammation in axial joints. In cultures, blocking PD-L1 removed the cells’ suppression of T-cell proliferation.[1]
Transferred precursors respond to local signals
Researchers followed marked precursor cells after transferring them to mice with arthritis, testing how the cells matured within tissue. CD200 blockade removed the benefit of those transferred cells. Human biopsies also linked a higher frequency of CD200-bearing supporting cells with lower patient-reported disease activity. Only limited tissue could be obtained from human axial joints, restricting direct functional tests. Human observations establish associations; interventions in animals and cultures test the mechanism. Clinical treatment benefit from restoring this pathway in patients remains unresolved.[1]
