Abstract
Dendritic cells (DCs) are crucial for initiating adaptive immune responses. However, the factors that control DC positioning and homeostasis are incompletely understood. We found that type-2 conventional DCs (cDC2s) in the spleen depend on Gα13 and adhesion G protein-coupled receptor family member-E5 (Adgre5, or CD97) for positioning in blood-exposed locations. CD97 function required its autoproteolytic cleavage. CD55 is a CD97 ligand, and cDC2 interaction with CD55-expressing red blood cells (RBCs) under shear stress conditions caused extraction of the regulatory CD97 N-terminal fragment. Deficiency in CD55-CD97 signaling led to loss of splenic cDC2s into the circulation and defective lymphocyte responses to blood-borne antigens. Thus, CD97 mechanosensing of RBCs establishes a migration and gene expression program that optimizes the antigen capture and presentation functions of splenic cDC2s.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Actins / metabolism
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Animals
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Antigen Presentation
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Antigens / immunology
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Blood Circulation
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CD55 Antigens / blood
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CD55 Antigens / metabolism
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Cell Movement
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Dendritic Cells / immunology
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Dendritic Cells / physiology*
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Erythrocytes / metabolism
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Erythrocytes / physiology*
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GTP-Binding Protein alpha Subunits, G12-G13 / metabolism
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Homeostasis
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Interferon Regulatory Factors / metabolism
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Ligands
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Mice
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Receptors, G-Protein-Coupled / genetics
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Receptors, G-Protein-Coupled / metabolism*
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Signal Transduction
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Spleen / blood supply
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Spleen / cytology*
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Spleen / immunology*
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Spleen / metabolism
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Transcription, Genetic
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Transcriptome
Substances
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Actins
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Adgre5 protein, mouse
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Antigens
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CD55 Antigens
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Interferon Regulatory Factors
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Ligands
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Receptors, G-Protein-Coupled
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interferon regulatory factor-4
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GTP-Binding Protein alpha Subunits, G12-G13