AIMp1 Potentiates T H 1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity

• Published in: Frontiers in immunology 2017, Vol.8, p.1801
• Main Authors: Liang, Dan, Tian, Lin, You, Ran, Halpert, Matthew M, Konduri, Vanaja, Baig, Yunyu C, Paust, Silke, Kim, Doyeun, Kim, Sunghoon, Jia, Fuli, Huang, Shixia, Zhang, Xiang, Kheradmand, Farrah, Corry, David B, Gilbert, Brian E, Levitt, Jonathan M, Decker, William K
• Format: Article
• Language: English
• ISSN: 1664-3224; 1664-3224

Dendritic cells (DCs) must integrate a broad array of environmental cues to exact control over downstream immune responses including T 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 T 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 T 1 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 . 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.