Related Experiment Video

Updated: Jun 4, 2026

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells
08:02

In Vivo Immunogenicity Screening of Tumor-Derived Extracellular Vesicles by Flow Cytometry of Splenic T Cells

Published on: September 23, 2021

PLA2G12A-driven extracellular vesicle-lipid signaling amplifies pathogenic T cell responses in inflammatory diseases

Chika Mochizuki-Ono1, Yoshitaka Taketomi1, Atsushi Irie2

  • 1Laboratory of Microenvironmental and Metabolic Health Sciences, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.

Cell Reports
|June 2, 2026
PubMed

Extracellular vesicles (EVs) contribute to intercellular communication, yet how EV-driven lipid signaling is regulated in immune responses remains incompletely understood. Here, we show that genetic deficiency or antibody-mediated neutralization of PLA2G12A, a secreted phospholipase A2 (sPLA2) transiently upregulated in activated CD4+ T cells, prevents pathogenic Th17 differentiation and associated diseases including psoriasis and arthritis. PLA2G12A acts on T cell-derived EVs to produce lysophospholipids including the RORγt activator 1-oleoyl-lysophosphatidylethanolamine. Furthermore, these lysophospholipids are converted by autotaxin to lysophosphatidic acid, which amplifies Th17 differentiation via the LPA2 receptor. Moreover, PLA2G12A promotes the secretion and uptake of EVs by Th17 cells and alters their cargo contents. Defective Th17 differentiation by PLA2G12A deficiency is restored by supplementation with PLA2G12A-modified EVs. These results provide a rationale for the sPLA2-EV-lysophospholipid axis as a general mode of sPLA2 action and suggest that targeting PLA2G12A may be useful for the treatment of Th17-related or possibly other inflammatory diseases.

Keywords:
CP: immunologyTh17 cellarthritisextracellular vesiclelipidomicslysophospholipidphospholipasepsoriasis

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