T Helper 17 Promotes Induction of Antigen-Specific Gut-Mucosal Cytotoxic T Lymphocytes following Adenovirus Vector Vaccination.
Masahisa Hemmi,Masashi Tachibana,Natsuki Fujimoto,Masaki Shoji,Fuminori Sakurai,Kouji Kobiyama,Ken Ishii,Shizuo Akira,Hiroyuki Mizuguchi +8 more
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TLDR
It is found that T helper 17 (Th17)-polarizing cytokine expression was down-regulated in the inguinal lymph nodes of Ifnar2−/− mice, resulting in the reduction of Ag-specific Th17 cells in the iLNs and gut mucosa of the mice, which could promote the development of promising Adv vaccines capable of establishing both systemic and gut-mucosal protective immunity.Abstract:
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.read more
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The protective and pathogenic roles of IL-17 in viral infections: friend or foe?
TL;DR: Accumulated experimental and clinical evidence has broadened the understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL- 17-targeted immunotherapy may be a promising therapeutic option.
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Adenovirus vector-based vaccine for infectious diseases
TL;DR: In this paper , the basic properties of an Ad vector, Ad vector induced innate immunity and immune responses to Ad vector-produced transgene products are described. And development of novel Ad vectors which can overcome the drawbacks of conventional Ad vector vaccines and clinical application of Ad vector vaccine to several infectious diseases are also discussed.
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Adenovirus vector-based vaccine for infectious diseases
TL;DR: In this article, the basic properties of an Ad vector, Ad vector induced innate immunity and immune responses to Ad vector-produced transgene products are described. And development of novel Ad vectors which can overcome the drawbacks of conventional Ad vector vaccines and clinical application of Ad vector vaccine to several infectious diseases are also discussed.
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In Vitro Th17-Polarized Human CD4+ T Cells Exacerbate Xenogeneic Graft-versus-Host Disease
Loïc Delens,Grégory Ehx,Joan Somja,Louise Vrancken,Ludovic Belle,Laurence Seidel,Céline Gregoire,Gilles Fransolet,Caroline Ritacco,Muriel Hannon,Sophie Dubois,Yves Beguin,Frédéric Baron,Sophie Servais +13 more
TL;DR: It is suggested that human Th17-polarized cells can cooperate with PBMCs and be pathogenic in the NSG xGVHD model.
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Is the oral microbiome a source to enhance mucosal immunity against infectious diseases
TL;DR: In this paper, the potential of oral commensals, and molecules derived thereof, to induce Th17 activity and provide safer and more predictable options in adjuvant engineering to prevent emerging infectious diseases.
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