Lack of phosphatidylinositol 3-kinase VPS34 in regulatory T cells leads to a fatal lymphoproliferative disorder without affecting their development

2024/11/27 by Christina J. F. Courrèges, Elizabeth C. M. Davenport, Benoît Bilanges +10 · 1 voice · 4 citations
Biochemistry, Genetics and Molecular Biology · Immunology and Microbiology · #Biology #Calcium signaling and nucleotide metabolism #Cancer research #Cell biology #Immune Cell Function and Interaction #Kinase #Phosphatidylinositol #T-cell and B-cell Immunology

paper · pdf · doi:10.3389/fimmu.2024.1374621

openalex publication_date 2024/11/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

Regulatory T (Treg) cells are essential for the maintenance of immunological tolerance, yet the molecular components required for their maintenance and effector functions remain incompletely defined. Inactivation of VPS34 in Treg cells led to an early, lethal phenotype, with massive effector T cell activation and inflammation, like mice lacking Treg cells completely. However, VPS34-deficient Treg cells developed normally, populated the peripheral lymphoid organs and effectively supressed conventional T cells in vitro . Our data suggest that VPS34 is required for the maintaining normal numbers of mature Treg. Functionally, we observed that lack of VPS34 activity impairs cargo processing upon transendocytosis, that defective autophagy may contribute to, but is not sufficient to explain this lethal phenotype, and that loss of VPS34 activity induces a state of heightened metabolic activity that may interfere with metabolic networks required for maintenance or suppressive functions of Treg cells.

Cited by

• Vps34-orchestrated lipid signaling processes regulate the transitional heterogeneity and functional adaptation of effector regulatory T cells. [europepmc]
• Vps34 puts the 'e' in eTreg cells. [europepmc]
• VPS34 in Autophagy, Cancer, and Cancer Therapy. [europepmc]
• Targeting regulatory T cells in glioblastoma: from mechanistic insights to novel immunotherapeutic strategies. [europepmc]

Discussions

• Our latest paper reveals an intriguing and essential role for the class III #PI3K VPS34 in Treg homeostasis and function. Selective deletion of VPS34 in Treg led to a scurfy-like phenotype, suggesting [bsky, 35 points, 1 comments]

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