 |
Article dans une revue
Inhibition of effector antigen-specific T cells by intradermal administration of heme oxygenase-1 inducers
Abstract : Developing protocols aimed at inhibiting effector T cells would be key for the treatment of T cell-dependent autoimmune diseases including type 1 autoimmune diabetes (T1D) and multiple sclerosis (MS). While heme oxygenase-1 (HO-1) inducers are clinically approved drugs for non-immune-related diseases, they do have immunosuppressive properties when administered systemically in rodents. Here we show that HO-1 inducers inhibit antigen-specific effector T cells when injected intradermally together with the T cell cognate antigens in mice. This phenomenon was observed in both a CD8 þ T cell-mediated model of T1D and in a CD4 þ T cell-dependent MS model. Intradermal injection of HO-1 in-ducers induced the recruitment of HO-1 þ monocyte-derived dendritic cell (MoDCs) exclusively to the lymph nodes (LN) draining the site of intradermal injection. After encountering HO-1 þ MoDCs, effector T-cells exhibited a lower velocity and a reduced ability to migrate towards chemokine gradients resulting in impaired accumulation to the inflamed organ. Intradermal co-injection of a clinically approved HO-1 inducer and a specific antigen to non-human primates also induced HO-1 þ MoDCs to accumulate in dermal draining LN and to suppress delayed-type hypersensitivity. Therefore, in both mice and non-human primates, HO-1 inducers delivered locally inhibited effector T-cells in an antigen-specific manner, paving the way for repositioning these drugs for the treatment of immune-mediated diseases.
Littérature citée [32 références]
https://www.hal.inserm.fr/inserm-01522579
Déposant : Elizabeth Bernardo <>
Soumis le : lundi 15 mai 2017 - 11:31:12
Dernière modification le : lundi 14 décembre 2020 - 15:38:55
Archivage à long terme le : : jeudi 17 août 2017 - 00:38:52
Déposant : Elizabeth Bernardo <>
Soumis le : lundi 15 mai 2017 - 11:31:12
Dernière modification le : lundi 14 décembre 2020 - 15:38:55
Archivage à long terme le : : jeudi 17 août 2017 - 00:38:52
Licence
Distributed under a Creative Commons Paternité - Partage selon les Conditions Initiales 4.0 International License
Données personnelles 
Mentions légales 