Completed Infection & Immunity Cells, Biochemistry & Physiology

The role of Eros in Innate and Adaptive Immunity

Funder Wellcome Charity-funded
Recipient organisation University of Cambridge
Funding £1.3M
Period Oct 2017 — Oct 2022

In plain English

AI plain-English summary

Mice lacking a single protein called Eros die from a common Salmonella infection because their immune cells cannot produce the bleach-like chemicals that kill bacteria. This matters because Eros is a newly discovered protein with a much wider role than first thought. It controls not only the immune system's ability to make reactive oxygen species—the chemical burst that destroys pathogens—but also regulates other key immune proteins and dramatically alters T cell behaviour. Eros-deficient T cells produce ten times more of the signalling molecule IL-4 than normal cells, suggesting Eros acts as a master switch for multiple immune functions. If this research succeeds, it will reveal the molecular mechanism by which Eros controls protein quality and immune signalling. This is fundamental science—there is no immediate medical application. But understanding how a single protein can orchestrate such broad immune responses could eventually point towards new ways to modulate the immune system in infections, autoimmune diseases, or allergies. Similar discoveries about unexpected immune regulators have repeatedly opened entirely new avenues for therapy.

View original technical description
I will investigate the role of a novel protein, Eros, in immunity. I discovered the fundamental importance of this protein by demonstrating that Eros-deficient mice die from Salmonella infection because their phagocytes cannot make reactive oxygen species. This is because Eros is essential for expression of vital components of the phagocyte NADPH oxidase. My work represents the only paper on this protein. I have found that Eros-deficiency has effects that go far beyond the generation of reactive oxygen species. In particular: • Eros regulates the expression of other key macrophage proteins including P2X7, a key activator of the NLRP3 inflammasome • Eros regulates the expression of numerous cytokines from CD4+ T cells. Eros -/- T cells make 10-fold more IL-4 than control cells In mouse and human systems, I will investigate the molecular mechanisms by which Eros: • controls the abundance of a subset of proteins working on the hypothesis that it is a novel component of the protein quality control pathway using structural, biochemical and cell biological techniques. • controls T cell cytokine secretion. I will spend time working with John O'Shea, a world leader in this field.

View the original record at the funder ↗

Researchers

David Thomas (EPMC Awardee)

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Original classification

Clinical Research Career Development Fellowship

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.