Autoren:	Sudowe, Stephan Höhn, Yvonne Renzing, Andrea Maxeiner, Joachim Montermann, Evelyn Habermeier, Alice Closs, Ellen Bros, Matthias Reske-Kunz, Angelika B.
Titel:	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-Publikationsdatum:	4-Jun-2021
Erscheinungsdatum:	2020
Sprache des Dokuments:	Englisch
Zusammenfassung/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-Sachgruppe:	610 Medizin 610 Medical sciences
Veröffentlichende Institution:	Johannes Gutenberg-Universität Mainz
Organisationseinheit:	FB 04 Medizin
Veröffentlichungsort:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-5971
Version:	Published version
Publikationstyp:	Zeitschriftenaufsatz
Nutzungsrechte:	CC BY
Informationen zu den Nutzungsrechten:	https://creativecommons.org/licenses/by/4.0/
Zeitschrift:	Amino acids 52
Seitenzahl oder Artikelnummer:	411 424
Verlag:	Springer
Verlagsort:	Wien u.a.
Erscheinungsdatum:	2020
ISSN:	1438-2199
URL der Originalveröffentlichung:	https://doi.org/10.1007/s00726-020-02817-4
DOI der Originalveröffentlichung:	10.1007/s00726-020-02817-4
Enthalten in den Sammlungen:	JGU-Publikationen