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Tolerogenic dendritic cell transfer ameliorates systemic lupus erythematosus in mice.
- Source :
-
Immunology [Immunology] 2019 Dec; Vol. 158 (4), pp. 322-339. Date of Electronic Publication: 2019 Oct 07. - Publication Year :
- 2019
-
Abstract
- Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Fas <superscript>lpr</superscript> and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60-70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Fas <superscript>lpr</superscript> lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.<br /> (© 2019 John Wiley & Sons Ltd.)
- Subjects :
- Animals
Antibodies, Antinuclear blood
Cell Differentiation
Cells, Cultured
Dendritic Cells transplantation
Dexamethasone metabolism
Disease Models, Animal
Humans
Immune Tolerance
Lupus Erythematosus, Systemic immunology
Lymphocyte Activation
Mice
Mice, Inbred MRL lpr
Pyrazines metabolism
Pyrroles metabolism
Rosiglitazone metabolism
Dendritic Cells immunology
Immunotherapy, Adoptive methods
Kidney pathology
Lupus Erythematosus, Systemic therapy
T-Lymphocytes, Regulatory immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2567
- Volume :
- 158
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31509246
- Full Text :
- https://doi.org/10.1111/imm.13119