Guest speaker David Thomas

Prof David Thomas MD PhD ( University of Cambridge, UK) will give a guest lecture at Sanquin Amsterdam on Tuesday 16 June 2026.

Title:  Reactive Oxygen Species: New insights into immunoregulation and host defence

Host: Iosifina Foskolou

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Reactive oxygen species produced by the phagocyte respiratory burst are essential for protection from infection but also for the prevention of autoimmunity and autoinflammation. EROS (encoded by CYBC1) is a transmembrane chaperone that we first identified as essential for the phagocyte respiratory burst. Using forward genetics in mice followed by human genetics and biochemical studies, we showed that EROS binds directly to the NADPH oxidase subunit gp91phox (NOX2/CYBB), stabilising the protein and enabling assembly of a functional oxidase complex. We and others showed that loss-of-function mutations in CYBC1 cause a previously unrecognised form of chronic granulomatous disease (CGD) characterised by impaired reactive oxygen species production and recurrent infections. More recently we discovered that EROS also functions as a highly selective chaperone for the ATP-gated purinergic receptor P2X7. In EROS-deficient mouse and human myeloid cells, P2X7 protein levels are profoundly reduced, resulting in defective calcium signalling, inflammasome activation and purinergic responses, independent of NADPH oxidase activity. These findings established an unexpected molecular link between oxidative burst and purinergic signalling pathways.

We have now identified a unique and previously unappreciated role for EROS in T cell biology. Using EROS-deficient mice, CRISPR-Cas9 edited primary human T cells, and T cells from patients carrying CYBC1 mutations, we have characterised how EROS regulates CD4+ T cell differentiation. In parallel, we have performed forward genetic screens and have uncovered novel regulators of both EROS and gp91phox expression. This has yielded unexpected insights into the cellular mechanisms that control NADPH oxidase assembly and stability.