AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity
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 ro...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01801/full |
| _version_ | 1818110742141861888 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Dan Liang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T02:51:59Z |
| format | Article |
| id | doaj.art-fea166d3121a45098c117454e94f8f59 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T02:51:59Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fea166d3121a45098c117454e94f8f592022-12-22T01:23:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-01-01810.3389/fimmu.2017.01801317628AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral ImmunityDan Liang0Lin Tian1Ran You2Matthew M. Halpert3Vanaja Konduri4Yunyu C. Baig5Silke Paust6Silke Paust7Silke Paust8Silke Paust9Silke Paust10Doyeun Kim11Sunghoon Kim12Fuli Jia13Fuli Jia14Fuli Jia15Shixia Huang16Shixia Huang17Shixia Huang18Xiang Zhang19Xiang Zhang20Xiang Zhang21Farrah Kheradmand22Farrah Kheradmand23David B. Corry24David B. Corry25Brian E. Gilbert26Jonathan M. Levitt27Jonathan M. Levitt28Jonathan M. Levitt29William K. Decker30William K. Decker31William K. Decker32Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pediatrics, Texas Children’s Hospital, Houston, TX, United StatesCenter for Human Immunobiology, Texas Children’s Hospital, Houston, TX, United StatesDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United StatesMedicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, South KoreaMedicinal Bioconvergence Research Center, Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University, Seoul, South KoreaDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United StatesAntibody-based Proteomics Core, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United StatesAntibody-based Proteomics Core, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United StatesLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States0Division of Pulmonary, Critical Care, and Sleep Medicine, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United States1Division of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States2Scott Department of Urology, Baylor College of Medicine, Houston, TX, United StatesDepartment of Pathology and Immunology, Baylor College of Medicine, Houston, TX, United StatesDan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, United States3Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, United StatesDendritic 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.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01801/fulldendritic cellAIMp1TH1 immunityIL-12antitumor immunityantiviral immunity |
| spellingShingle | 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 AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity Frontiers in Immunology dendritic cell AIMp1 TH1 immunity IL-12 antitumor immunity antiviral immunity |
| title | AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity |
| title_full | AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity |
| title_fullStr | AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity |
| title_full_unstemmed | AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity |
| title_short | AIMp1 Potentiates TH1 Polarization and Is Critical for Effective Antitumor and Antiviral Immunity |
| title_sort | aimp1 potentiates th1 polarization and is critical for effective antitumor and antiviral immunity |
| topic | dendritic cell AIMp1 TH1 immunity IL-12 antitumor immunity antiviral immunity |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01801/full |
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