Spondyloarthritis & psoriatic arthritis

Healthy human enthesis stromal cells mediate immunoregulation via the CD39/CD73 adenosine ectonucleotidase pathway

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

The normal spinal enthesis harbours an immunoregulatory cellular environment related to entheseal MSCs that utilises the CD39/CD73 adenosine ectonucleotidase axis that may help maintain local immune homeostasis, while the same adenosine ectonucleotidase immunoregulatory pathway is likely dependent on Treg function in the intestine.

Study context

Population
Healthy human entheseal tissue (normal spinal enthesis), compared with intestinal tissue datasets
Participants
27,348 entheseal cells
Comparison
Enthesis vs Ileum vs Colon
Outcome
Treg frequency among T cells
Methodological detailssingle-cell RNA sequencing, comparative transcriptomic analysis with intestinal tissue datasets, coculture with activated T cells, pharmacological inhibition
  • Single-cell RNA sequencing
  • Comparative transcriptomic analysis with intestinal tissue datasets
  • Coculture with activated T cells
  • Pharmacological inhibition

Main finding

As reported in the abstract

Entheseal mesenchymal stromal cells (MSCs) suppressed T cell proliferation in an adenosine-dependent manner (up to)
89%, P < .0001
Dual CD39/CD73 inhibition restored T cell proliferation by
∼48% (P = .0004)

Original publication

Healthy human enthesis stromal cells mediate immunoregulation via the CD39/CD73 adenosine ectonucleotidase pathway. Ann Rheum Dis. Published 6 October 2025. doi:10.1016/j.ard.2025.09.001

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