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CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells.

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.

SUBMITTER: Liu D 

PROVIDER: S-EPMC9310086 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells.

Liu Dan D   Duan Lihui L   Rodda Lauren B LB   Lu Erick E   Xu Ying Y   An Jinping J   Qiu Longhui L   Liu Fengchun F   Looney Mark R MR   Yang Zhiyong Z   Allen Christopher D C CDC   Li Zhongmei Z   Marson Alexander A   Cyster Jason G JG  

Science (New York, N.Y.) 20220211 6581

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 Gα<sub>13</sub> 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 blo  ...[more]

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