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Immunity. 2015 Oct 20;43(4):764-75. doi: 10.1016/j.immuni.2015.08.021. Epub 2015 Oct 6.

Splenic Dendritic Cells Survey Red Blood Cells for Missing Self-CD47 to Trigger Adaptive Immune Responses.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
2
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94141, USA.
3
Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA. Electronic address: jason.cyster@ucsf.edu.

Abstract

Sheep red blood cells (SRBCs) have long been used as a model antigen for eliciting systemic immune responses, yet the basis for their adjuvant activity has been unknown. Here, we show that SRBCs failed to engage the inhibitory mouse SIRPα receptor on splenic CD4(+) dendritic cells (DCs), and this failure led to DC activation. Removal of the SIRPα ligand, CD47, from self-RBCs was sufficient to convert them into an adjuvant for adaptive immune responses. DC capture of Cd47(-/-) RBCs and DC activation occurred within minutes in a Src-family-kinase- and CD18-integrin-dependent manner. These findings provide an explanation for the adjuvant mechanism of SRBCs and reveal that splenic DCs survey blood cells for missing self-CD47, a process that might contribute to detecting and mounting immune responses against pathogen-infected RBCs.

PMID:
26453377
PMCID:
PMC4618158
DOI:
10.1016/j.immuni.2015.08.021
[Indexed for MEDLINE]
Free PMC Article

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