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Front Immunol. 2018 Jan 15;8:1801. doi: 10.3389/fimmu.2017.01801. eCollection 2017.

AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity.

Liang D1, Tian L2, You R1, Halpert MM1, Konduri V1, Baig YC1, Paust S1,3,4,5,6, Kim D7, Kim S7, Jia F2,6,8, Huang S2,6,8, Zhang X2,6,9, Kheradmand F1,10, Corry DB1,11, Gilbert BE5, Levitt JM1,6,12, Decker WK1,6,13.

Author information

1
Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States.
2
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United States.
3
Department of Pediatrics, Texas Children's Hospital, Houston, TX, United States.
4
Center for Human Immunobiology, Texas Children's Hospital, Houston, TX, United States.
5
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United States.
6
Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States.
7
Medicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, South Korea.
8
Antibody-based Proteomics Core, Baylor College of Medicine, Houston, TX, United States.
9
Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United States.
10
Division of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX, United States.
11
Division of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, TX, United States.
12
Scott Department of Urology, Baylor College of Medicine, Houston, TX, United States.
13
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United States.

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:

AIMp1; IL-12; TH1 immunity; antitumor immunity; antiviral immunity; dendritic cell; p38 MAPK signaling

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