Vasculitis & polymyalgia rheumatica
Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production
Authors' conclusion
Myelomonocytic cells in GCA activate TI programs sustaining enhanced inflammatory activation with excess cytokine production.
Study context
- Population
- Patients with giant cell arteritis (GCA) and age- and sex-matched healthy donors
- Comparison
- GCA monocytes vs age- and sex-matched healthy donor monocytes
- Outcome
- Hallmark molecular features of trained immunity (TI) in GCA monocytes
Methodological detailsage- and sex-matched healthy donors, Cytokine production assays at baseline and after stimulation, intracellular metabolomics, ChIP-qPCR, combined ATAC/RNA sequencing; FDG-PET and immunohistochemistry of inflamed vessels; selective pharmacologic inhibition of glycolysis in GCA monocytes
- Age- and sex-matched healthy donors
- Cytokine production assays at baseline and after stimulation, intracellular metabolomics, ChIP-qPCR, combined ATAC/RNA sequencing; FDG-PET and immunohistochemistry of inflamed vessels; selective pharmacologic inhibition of glycolysis in GCA monocytes
Main finding
As reported in the abstract
- Enhanced IL-6 production upon stimulation in GCA monocytes
- Typical immunometabolic changes (e.g. increased glycolysis and glutaminolysis)
- Epigenetic changes promoting enhanced transcription of genes governing pro-inflammatory activation
- Glycolysis a feature of myelomonocytic cells in GCA lesions and required for enhanced cytokine production
Original publication
Myelomonocytic cells in giant cell arteritis activate trained immunity programs sustaining inflammation and cytokine production. Rheumatology (Oxford). Published 20 February 2023. doi:10.
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