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Inhibition of effector antigen-specific T cells by intradermal administration of heme oxygenase-1 inducers
- Source :
- Journal of Autoimmunity, Journal of Autoimmunity, Elsevier, 2017, 81, pp.44-55. 〈10.1016/j.jaut.2017.03.005〉, Journal of Autoimmunity, Elsevier, 2017, 81, pp.44-55. ⟨10.1016/j.jaut.2017.03.005⟩, Journal of Autoimmunity, 2017, 81, pp.44-55. ⟨10.1016/j.jaut.2017.03.005⟩
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- International audience; 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.
- Subjects :
- CD4-Positive T-Lymphocytes
0301 basic medicine
T-lymphocyte
Chemokine
T-Lymphocytes
T cell
Immunology
Antigen-Presenting Cells
Mice, Transgenic
T-Cell Antigen Receptor Specificity
[SDV.CAN]Life Sciences [q-bio]/Cancer
Autoimmunity
Autoantigens
Autoimmune Diseases
[ SDV.CAN ] Life Sciences [q-bio]/Cancer
Mice
03 medical and health sciences
[SDV.CAN] Life Sciences [q-bio]/Cancer
Antigen
medicine
Animals
Humans
Immunology and Allergy
Hypersensitivity, Delayed
Intradermal injection
Antigens
Migration
biology
Effector
Diabetes
Dendritic cell
Papio anubis
Auto-immune encephalomyelitis
Delayed type hypersensitivity
3. Good health
Heme oxygenase
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Heme oxygenase-1
biology.protein
Cytokines
Immunization
Myelin-Oligodendrocyte Glycoprotein
Tolerance
Monocyte-derived dendritic cells
CD8
T-Lymphocytes, Cytotoxic
Subjects
Details
- ISSN :
- 08968411 and 10959157
- Volume :
- 81
- Database :
- OpenAIRE
- Journal :
- Journal of Autoimmunity
- Accession number :
- edsair.doi.dedup.....0562a45c197d4b1708dd1fc282812b38