Multi-enzyme aminoacyl tRNA synthetase complex component AIMp1/p43 as an important Th1 mediator (IRC7P.428)
| Autor: | Dan Liang, Matthew Halpert, Vanaja Konduri, Yunyu Chen, Doyeun Kim, Sunghoon Kim, Jonathan Levitt, William Decker |
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| Rok vydání: | 2015 |
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| Zdroj: | The Journal of Immunology. 194:128.9-128.9 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.194.supp.128.9 |
| Popis: | Of professional antigen presenting cells, only the dendritic cells (DC) are regarded as initiators of adaptive immune responses. Previously we identified a Th1 polarizing phenotype from DCs loaded with overlapping (homologous) MHC class I and II determinants, including augmented DC IL-12 production, generation of CD8+ cytolytic effectors, and T cell IFNγ secretion, suggesting DC intrinsic mechanisms to recognize and compare antigenic epitopes. AIMp1/p43 is a structural component of the multi-enzyme aminoacyl-tRNA synthetase complex (mARS) and indicated by previous studies to be a pro-inflammatory cytokine. We identified high levels of p43 release correlated with degree of homology between antigenic epitopes on DC class I and II molecules. In vitro studies confirmed p43 deficiency impairs DC costimulatory and Th1 polarizing functions. It also reversely regulates the production of IFNγ and IL4 within T cells. In vivo, p43 deficiency abolishes the ability of DC to mediate effective response against B16 melanoma tumors, and leads to higher susceptibility to influenza viral infections. These data support our hypothesis that p43 is a critical Th1 polarizing effector molecule. We will investigate further into p43 functions in DC and T cell crosstalk, targeting candidate cell surface receptors and intracellular signaling pathways. Additionally, we will better characterize in vivo roles of p43 in anti-tumor and anti-viral models and seek to apply it as a novel vaccination adjuvant. |
| Databáze: | OpenAIRE |
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