Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-5971
Authors: | Sudowe, Stephan Höhn, Yvonne Renzing, Andrea Maxeiner, Joachim Montermann, Evelyn Habermeier, Alice Closs, Ellen Bros, Matthias Reske-Kunz, Angelika B. |
Title: | Inhibition of antigen-specific immune responses by co-application of an indoleamine 2,3-dioxygenase (IDO)-encoding vector requires antigen transgene expression focused on dendritic cells |
Online publication date: | 4-Jun-2021 |
Year of first publication: | 2020 |
Language: | english |
Abstract: | We have previously shown that particle-mediated epidermal delivery (PMED) of plasmids encoding β-galactosidase (βGal) under control of the fascin-1 promoter (pFascin-βGal) yielded selective production of the protein in skin dendritic cells (DCs), and suppressed Th2 responses in a mouse model of type I allergy by inducing Th1/Tc1 cells. However, intranasal challenge of mice immunized with pFascin-βGal induced airway hyperreactivity (AHR) and neutrophilic inflammation in the lung. The tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) has been implicated in immune suppression and tolerance induction. Here we investigated the consequences of co-application of an IDO-encoding vector on the modulatory effect of DNA vaccination by PMED using pFascin-βGal in models of eosinophilic allergic and non-eosinophilic intrinsic airway inflammation. IDO-encoding plasmids and pFascin-βGal or pCMV-βGal were co-applied to abdominal skin of BALB/c mice without, before or after sensitization with βGal protein. Immune responses in the lung were analysed after intranasal provocation and airway reactivity was determined by whole body plethysmography. Co-application of pCMV-IDO with pFascin-βGal, but not pCMV-βGal inhibited the Th1/Tc1 immune response after PMED. Moreover, AHR in those mice was attenuated following intranasal challenge. Therapeutic vaccination of βGal-sensitized mice with pFascin-βGal plus pCMV-IDO slightly suppressed airway inflammation and AHR after provocation with βGal protein, while prophylactic vaccination was not effective. Altogether, our data suggest that only the combination of DC-restricted antigen and ubiquitous IDO expression attenuated asthma responses in mice, most probably by forming a tryptophan-depleted and kynurenine-enriched micromilieu known to affect neutrophils and T cells. |
DDC: | 610 Medizin 610 Medical sciences |
Institution: | Johannes Gutenberg-Universität Mainz |
Department: | FB 04 Medizin |
Place: | Mainz |
ROR: | https://ror.org/023b0x485 |
DOI: | http://doi.org/10.25358/openscience-5971 |
Version: | Published version |
Publication type: | Zeitschriftenaufsatz |
License: | CC BY |
Information on rights of use: | https://creativecommons.org/licenses/by/4.0/ |
Journal: | Amino acids 52 |
Pages or article number: | 411 424 |
Publisher: | Springer |
Publisher place: | Wien u.a. |
Issue date: | 2020 |
ISSN: | 1438-2199 |
Publisher URL: | https://doi.org/10.1007/s00726-020-02817-4 |
Publisher DOI: | 10.1007/s00726-020-02817-4 |
Appears in collections: | JGU-Publikationen |
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File | Description | Size | Format | ||
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sudowe_stephan-inhibition_of_-20210527012518964.pdf | 1.29 MB | Adobe PDF | View/Open |