title: Splenic Dendritic Cells Survey Red Blood Cells for Missing Self-CD47 to Trigger Adaptive Immune Responses.
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.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
authors.forename: Tangsheng
authors.initials: T
authors.lastname: Yi
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
authors.forename: Hsin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
authors.forename: Jinping
authors.initials: J
authors.lastname: An
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94141, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94141, USA.
authors.forename: Clifford A
authors.initials: CA
authors.lastname: Lowell
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco and Howard Hughes Medical Institute, CA 94143, USA. Electronic address: jason.cyster@ucsf.edu.
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic; D000818:Animals; D001483:Base Sequence; D018821:CD18 Antigens / Q000502:physiology; D015704:CD4 Antigens / Q000032:analysis; D051928:CD47 Antigen / Q000097:blood* / Q000276:immunology; D002465:Cell Movement; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology*; D016023:Integrins / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011828:Radiation Chimera; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology*; D017634:Self Tolerance / Q000276:immunology*; D012756:Sheep; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019061:src-Family Kinases / Q000172:deficiency / Q000502:physiology
chemical_list: D000276:Adjuvants, Immunologic; D018821:CD18 Antigens; D015704:CD4 Antigens; D051928:CD47 Antigen; C497895:Cd47 protein, mouse; D016023:Integrins; C501922:Sirpa protein, mouse; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D019061:src-Family Kinases