Dendritic cells (DCs) must integrate a broad array of environmental cues to exact control over downstream immune responses including TH polarization. The multienzyme aminoacyl-tRNA synthetase complex component AIMp1/p43 responds to cellular stress and exerts pro-inflammatory functions; however, a role for DC-expressed AIMp1 in TH polarization has not previously been shown. Here, we demonstrate that the absence of AIMp1 in bone marrow-derived DC (BMDC) significantly impairs cytokine and costimulatory molecule expression, p38 MAPK signaling, and TH1 polarization of cocultured T-cells while significantly dysregulating immune-related gene expression. These deficits resulted in significantly compromised BMDC vaccine-mediated protection against melanoma. AIMp1 within the host was also critical for innate and adaptive antiviral immunity against influenza virus infection in vivo. Cancer patients with AIMp1 expression levels in the highest tertiles exhibited a 70% survival advantage at 15-year postdiagnosis as determined by bioinformatics analysis of nearly 9,000 primary human tumor samples in The Cancer Genome Atlas database. These data establish the importance of AIMp1 for the effective governance of antitumor and antiviral immune responses.
Bibliographical noteFunding Information:
This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (P30 AI036211, P30 CA125123, and S10 RR024574) and the expert assistance of Joel M. Sederstrom; the Proteomics and Metabolomics Core Facility at Baylor College of Medicine with funding from the Cancer Prevention and Research Institute of Texas (RP170005) and from NCI P30 Grant (CA123125); the Sequencing and Microarray Facility at MD Anderson Cancer Center with funding from the NIH to SF (CA016672). Additional funding was provided by a Reach Award from Alex's Lemonade Stand Childhood Cancer Foundation (to WD). This work was also made possible by the CyVerse Collaborative, funded by the NSF (DBI-0735191). The authors declare no financial conflicts of interest.
© 2018 Liang, Tian, You, Halpert, Konduri, Baig, Paust, Kim, Kim, Jia, Huang, Zhang, Kheradmand, Corry, Gilbert, Levitt and Decker.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy