T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination
Few current vaccines can establish antigen (Ag)-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adeno...
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Frontiers Media S.A.
2017-11-01
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Series: | Frontiers in Immunology |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01456/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Masahisa Hemmi Masashi Tachibana Masashi Tachibana Masashi Tachibana Natsuki Fujimoto Masaki Shoji Fuminori Sakurai Fuminori Sakurai Kouji Kobiyama Kouji Kobiyama Ken J. Ishii Ken J. Ishii Shizuo Akira Shizuo Akira Hiroyuki Mizuguchi Hiroyuki Mizuguchi Hiroyuki Mizuguchi Hiroyuki Mizuguchi |
spellingShingle |
Masahisa Hemmi Masashi Tachibana Masashi Tachibana Masashi Tachibana Natsuki Fujimoto Masaki Shoji Fuminori Sakurai Fuminori Sakurai Kouji Kobiyama Kouji Kobiyama Ken J. Ishii Ken J. Ishii Shizuo Akira Shizuo Akira Hiroyuki Mizuguchi Hiroyuki Mizuguchi Hiroyuki Mizuguchi Hiroyuki Mizuguchi T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination Frontiers in Immunology T helper 17 cells cytotoxic T lymphocyte vaccines DNA vaccines mucosal immunity gut mucosa |
author_facet |
Masahisa Hemmi Masashi Tachibana Masashi Tachibana Masashi Tachibana Natsuki Fujimoto Masaki Shoji Fuminori Sakurai Fuminori Sakurai Kouji Kobiyama Kouji Kobiyama Ken J. Ishii Ken J. Ishii Shizuo Akira Shizuo Akira Hiroyuki Mizuguchi Hiroyuki Mizuguchi Hiroyuki Mizuguchi Hiroyuki Mizuguchi |
author_sort |
Masahisa Hemmi |
title |
T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination |
title_short |
T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination |
title_full |
T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination |
title_fullStr |
T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination |
title_full_unstemmed |
T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination |
title_sort |
t helper 17 promotes induction of antigen-specific gut-mucosal cytotoxic t lymphocytes following adenovirus vector vaccination |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-11-01 |
description |
Few current vaccines can establish antigen (Ag)-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv) has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs) in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN) signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17)-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs) of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2−/− mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity. |
topic |
T helper 17 cells cytotoxic T lymphocyte vaccines DNA vaccines mucosal immunity gut mucosa |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01456/full |
work_keys_str_mv |
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doaj-72d07055fe6e4762b51b2375f9b474a72020-11-24T22:51:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-11-01810.3389/fimmu.2017.01456300761T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector VaccinationMasahisa Hemmi0Masashi Tachibana1Masashi Tachibana2Masashi Tachibana3Natsuki Fujimoto4Masaki Shoji5Fuminori Sakurai6Fuminori Sakurai7Kouji Kobiyama8Kouji Kobiyama9Ken J. Ishii10Ken J. Ishii11Shizuo Akira12Shizuo Akira13Hiroyuki Mizuguchi14Hiroyuki Mizuguchi15Hiroyuki Mizuguchi16Hiroyuki Mizuguchi17Laboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanGlobal Center for Medical Engineering and Informatics, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanLaboratory of Regulatory Sciences for Oligonucleotide Therapeutics, Clinical Drug Development Unit, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanCenter for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, JapanLaboratory of Vaccine Science, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka, JapanCenter for Vaccine and Adjuvant Research, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, JapanLaboratory of Vaccine Science, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka, JapanLaboratory of Host Defense, World Premier International Research Center Immunology Frontier Research Center, Osaka University, Osaka, JapanDepartment of Host Defense, The Research Institute for Microbial Diseases, Osaka University, Osaka, JapanLaboratory of Biochemistry and Molecular Biology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, JapanGlobal Center for Medical Engineering and Informatics, Osaka University, Osaka, JapaniPS Cell-Based Research Project on Hepatic Toxicity and Metabolism, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan0Laboratory of Hepatocyte Regulation, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka, JapanFew current vaccines can establish antigen (Ag)-specific immune responses in both mucosal and systemic compartments. Therefore, development of vaccines providing defense against diverse infectious agents in both compartments is of high priority in global health. Intramuscular vaccination of an adenovirus vector (Adv) has been shown to induce Ag-specific cytotoxic T lymphocytes (CTLs) in both systemic and gut-mucosal compartments. We previously found that type I interferon (IFN) signaling is required for induction of gut-mucosal, but not systemic, CTLs following vaccination; however, the molecular mechanism involving type I IFN signaling remains unknown. Here, we found that T helper 17 (Th17)-polarizing cytokine expression was down-regulated in the inguinal lymph nodes (iLNs) of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice. We also found that prior transfer of Th17 cells reversed the decrease in the number of Ag-specific gut-mucosal CTLs in Ifnar2−/− mice following Adv vaccination. Additionally, prior transfer of Th17 cells into wild-type mice enhanced the induction of Ag-specific CTLs in the gut mucosa, but not in systemic compartments, suggesting a gut mucosa-specific mechanism where Th17 cells regulate the magnitude of vaccine-elicited Ag-specific CTL responses. These data suggest that Th17 cells translate systemic type I IFN signaling into a gut-mucosal CTL response following vaccination, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01456/fullT helper 17 cellscytotoxic T lymphocytevaccinesDNA vaccinesmucosal immunitygut mucosa |