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IRAP Endosomes Control Phagosomal Maturation in Dendritic Cells.
Mirjana Weimershaus1, François-Xavier Mauvais1, Irini Evnouchidou1,2
1Institut National de la Santé et de la Recherche Médicale, Unité 1151, Université de Paris, Centre National de la Recherche Scientifique, UMR 8253, Paris, France.
Frontiers in Cell and Developmental Biology
|January 11, 2021
Summary
Insulin-regulated aminopeptidase (IRAP) is crucial for dendritic cell (DC) immune surveillance. IRAP regulates phagosome maturation and antigen cross-presentation, essential for CD8+ T cell responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Dendritic cells (DCs) are key immune sentinels, sampling antigens via phagocytosis and endocytosis.
- A specialized endosomal compartment, marked by Rab14 and insulin-regulated aminopeptidase (IRAP), regulates antigen processing and cross-presentation to CD8+ T cells.
Purpose of the Study:
- To investigate the role of IRAP in modulating phagosome maturation dynamics and antigen cross-presentation in DCs.
- To elucidate the dual function of IRAP as a peptidase and a factor in endosome stability.
Main Methods:
- Utilized IRAP knockout (IRAP-/-) DCs to study phagosome maturation and cross-presentation.
- Employed protease-dead IRAP mutants and pharmacological inhibition to assess IRAP's proteolytic activity.
- Investigated vesicle trafficking from the ER-Golgi intermediate compartment to endosomes.
Main Results:
- IRAP deficiency leads to accelerated phagosome maturation, increased degradative capacity, and enhanced microbicidal activity.
- Evidence suggests ER-Golgi intermediate compartment vesicle trafficking is vital for IRAP compartment formation/stability.
- IRAP expression, not its proteolytic activity, is essential for storage endosome formation and typical DC phagosome maturation.
Conclusions:
- IRAP plays a critical role in antigen cross-presentation by stabilizing endosomes and trimming peptides for MHC class I binding.
- Proteolytic activity of IRAP is required for efficient cross-presentation, while its structural role is key for phagosome maturation.
- IRAP acts as a crucial regulator, balancing antigen degradation and presentation for effective T cell immunity.
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