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; Doyeun Kim; Sunghoon Kim; Fuli Jia; Shixia Huang; Xiang Zhang; Farrah Kheradmand; David B. Corry; Brian E. Gilbert; Jonathan M. Levitt; William K. Decker

doi:10.3389/fimmu.2017.01801

AIMp1 potentiates T_H1 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, Doyeun Kim, Sunghoon Kim, Fuli Jia, Shixia Huang, Xiang Zhang, Farrah Kheradmand, David B. Corry, Brian E. Gilbert, Jonathan M. Levitt, William K. Decker

Department of Pharmacy

Research output: Contribution to journal › Article › peer-review

22 Citations (Scopus)

Abstract

Dendritic cells (DCs) must integrate a broad array of environmental cues to exact control over downstream immune responses including T_H 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_H 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_H1 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.

Original language	English
Article number	1801
Journal	Frontiers in Immunology
Volume	8
Issue number	JAN
DOIs	https://doi.org/10.3389/fimmu.2017.01801
Publication status	Published - 2018 Jan 15

Bibliographical note

Funding 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.

Publisher Copyright:
© 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
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3389/fimmu.2017.01801

Cite this

Liang, D., Tian, L., You, R., Halpert, M. M., Konduri, V., Baig, Y. C., Paust, S., Kim, D., Kim, S., Jia, F., Huang, S., Zhang, X., Kheradmand, F., Corry, D. B., Gilbert, B. E., Levitt, J. M., & Decker, W. K. (2018). AIMp1 potentiates T_H1 polarization and is critical for effective antitumor and antiviral immunity. Frontiers in Immunology, 8(JAN), [1801]. https://doi.org/10.3389/fimmu.2017.01801

@article{4551a53d0b8d46a1be41b9d57f9fc643,

title = "AIMp1 potentiates TH1 polarization and is critical for effective antitumor and antiviral immunity",

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.",

author = "Dan Liang and Lin Tian and Ran You and Halpert, {Matthew M.} and Vanaja Konduri and Baig, {Yunyu C.} and Silke Paust and Doyeun Kim and Sunghoon Kim and Fuli Jia and Shixia Huang and Xiang Zhang and Farrah Kheradmand and Corry, {David B.} and Gilbert, {Brian E.} and Levitt, {Jonathan M.} and Decker, {William K.}",

note = "Funding 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. Publisher Copyright: {\textcopyright} 2018 Liang, Tian, You, Halpert, Konduri, Baig, Paust, Kim, Kim, Jia, Huang, Zhang, Kheradmand, Corry, Gilbert, Levitt and Decker.",

year = "2018",

month = jan,

day = "15",

doi = "10.3389/fimmu.2017.01801",

language = "English",

volume = "8",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S. A.",

number = "JAN",

}

Liang, D, Tian, L, You, R, Halpert, MM, Konduri, V, Baig, YC, Paust, S, Kim, D, Kim, S, Jia, F, Huang, S, Zhang, X, Kheradmand, F, Corry, DB, Gilbert, BE, Levitt, JM & Decker, WK 2018, 'AIMp1 potentiates T_H1 polarization and is critical for effective antitumor and antiviral immunity', Frontiers in Immunology, vol. 8, no. JAN, 1801. https://doi.org/10.3389/fimmu.2017.01801

TY - JOUR

T1 - AIMp1 potentiates TH1 polarization and is critical for effective antitumor and antiviral immunity

AU - Liang, Dan

AU - Tian, Lin

AU - You, Ran

AU - Halpert, Matthew M.

AU - Konduri, Vanaja

AU - Baig, Yunyu C.

AU - Paust, Silke

AU - Kim, Doyeun

AU - Kim, Sunghoon

AU - Jia, Fuli

AU - Huang, Shixia

AU - Zhang, Xiang

AU - Kheradmand, Farrah

AU - Corry, David B.

AU - Gilbert, Brian E.

AU - Levitt, Jonathan M.

AU - Decker, William K.

N1 - Funding 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. Publisher Copyright: © 2018 Liang, Tian, You, Halpert, Konduri, Baig, Paust, Kim, Kim, Jia, Huang, Zhang, Kheradmand, Corry, Gilbert, Levitt and Decker.

PY - 2018/1/15

Y1 - 2018/1/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85040843843&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040843843&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2017.01801

DO - 10.3389/fimmu.2017.01801

M3 - Article

AN - SCOPUS:85040843843

SN - 1664-3224

VL - 8

JO - Frontiers in Immunology

JF - Frontiers in Immunology

IS - JAN

M1 - 1801

ER -