Frontiers in Immunology (Jan 2018)
AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity
- Dan Liang,
- Lin Tian,
- Ran You,
- Matthew M. Halpert,
- Vanaja Konduri,
- Yunyu C. Baig,
- Silke Paust,
- Silke Paust,
- Silke Paust,
- Silke Paust,
- Silke Paust,
- Doyeun Kim,
- Sunghoon Kim,
- Fuli Jia,
- Fuli Jia,
- Fuli Jia,
- Shixia Huang,
- Shixia Huang,
- Shixia Huang,
- Xiang Zhang,
- Xiang Zhang,
- Xiang Zhang,
- Farrah Kheradmand,
- Farrah Kheradmand,
- David B. Corry,
- David B. Corry,
- Brian E. Gilbert,
- Jonathan M. Levitt,
- Jonathan M. Levitt,
- Jonathan M. Levitt,
- William K. Decker,
- William K. Decker,
- William K. Decker
Affiliations
- Dan Liang
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Lin Tian
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
- Ran You
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Matthew M. Halpert
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Vanaja Konduri
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Yunyu C. Baig
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Silke Paust
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Silke Paust
- Department of Pediatrics, Texas Children’s Hospital, Houston, TX, United States
- Silke Paust
- Center for Human Immunobiology, Texas Children’s Hospital, Houston, TX, United States
- Silke Paust
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States
- Silke Paust
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
- Doyeun Kim
- Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, South Korea
- Sunghoon Kim
- Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, South Korea
- Fuli Jia
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
- Fuli Jia
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
- Fuli Jia
- Antibody-based Proteomics Core, Baylor College of Medicine, Houston, TX, United States
- Shixia Huang
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
- Shixia Huang
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
- Shixia Huang
- Antibody-based Proteomics Core, Baylor College of Medicine, Houston, TX, United States
- Xiang Zhang
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States
- Xiang Zhang
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
- Xiang Zhang
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States
- Farrah Kheradmand
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Farrah Kheradmand
- 0Division of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX, United States
- David B. Corry
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- David B. Corry
- 1Division of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, TX, United States
- Brian E. Gilbert
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States
- Jonathan M. Levitt
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- Jonathan M. Levitt
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
- Jonathan M. Levitt
- 2Scott Department of Urology, Baylor College of Medicine, Houston, TX, United States
- William K. Decker
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States
- William K. Decker
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States
- William K. Decker
- 3Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States
- DOI
- https://doi.org/10.3389/fimmu.2017.01801
- Journal volume & issue
-
Vol. 8
Abstract
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.
Keywords
