Stepping Out of the Cytosol: AIMp1/p43 Potentiates the Link Between Innate and Adaptive Immunity.
As a structural component of the multi-aminoacyl tRNA synthetase (mARS) complex, AIMp1, also known as p43, hasn't until recently been recognized for its prominent immunological functions. Together with other nonenzymatic mARS structural components AIMp2/38 and AIMp3/p18, it participates in the machinery responsible for cell-cycle control and tumor suppression. Novel studies also show that AIMp1/p43 can be released by certain cancer cells under conditions of stress. Extracellularly, AIMp1 promotes the proliferation and migration of fibroblasts/endothelial cells and importantly, pro-inflammatory gene expression in monocytes/macrophages and dendritic cells. AIMp1/p43 deficiency is also correlated with spontaneous Type-2 airway hypersensitivity in mice, indicating a potential role in skewing toward T-helper type-1 (T(H)1) immunity. Vaccination strategies in which dendritic cells receive dual MHC class I and MHC class II antigens of homologous origins (i.e., that share overlapping class I and II binding epitopes) boost downstream T(H)1 immunity in a manner that appears to be wholly dependent upon dendritic cell AIMp1 release. Here we underscore the importance of AIMp1/p43 as a pro-inflammatory cytokine when it is released from cytosol to extracellular space and discuss future directions by which the mechanisms that regulate this process might be better characterized, further elucidating the link between innate and adaptive immunity.
a Department of Pathology & Immunology , Baylor College of Medicine , One Baylor Plaza, Houston , TX , USA.
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a Department of Pathology & Immunology , Baylor College of Medicine , One Baylor Plaza, Houston , TX , USA.
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a Department of Pathology & Immunology , Baylor College of Medicine , One Baylor Plaza, Houston , TX , USA.
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a Department of Pathology & Immunology , Baylor College of Medicine , One Baylor Plaza, Houston , TX , USA.|b Center for Cell and Gene Therapy , Baylor College of Medicine , One Baylor Plaza, Houston , TX , USA.|c Dan L. Duncan Cancer Center , One Baylor Plaza, Houston , TX , USA.
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D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D059447:Cell Cycle Checkpoints / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D003600:Cytosol / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology; D010445:Peptide Elongation Factors / Q000276:immunology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000276:immunology
C575685:AIMP2 protein, human; D016207:Cytokines; C529799:EEF1E1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C077219:small inducible cytokine subfamily E, member 1
AIMp1; TH1 immunity; multiaminoacyl–tRNA synthetase complex