Abstract
Experimental allergic encephalomyelitis (EAE) can be induced in animal models by injecting the MOG35-55 peptide subcutaneously. Dendritic cells (DCs) that are located at the immunization site phagocytose the MOG35-55 peptide. These DCs mature and migrate into the nearest draining lymph nodes (dLNs), then present antigen, resulting in the activation of naive T cells. T helper type 1 (Th1) and Th17 cells are the primary cells involved in EAE progression. All-trans-retinoic acid (AT-RA) has been shown to have beneficial effects on EAE progression; however, whether AT-RA influences DC maturation or mediates other functions is unclear. In the present study, we showed that AT-RA led to the down-regulation of MHC class II, CD80 (B7-1) and CD86 (B7-2) expressed on the surface of DCs that were isolated from dLNs or spleen 3 days post-immunization in an EAE model. Changes to DC function influenced Th1/Th17 subset polarization. Furthermore, the number of CD44(+) monocytes (which might trigger EAE progression) was also significantly decreased in dLNs, spleen, subarachnoid space and the spinal cord parenchyma after AT-RA treatment. These findings are the first to demonstrate that AT-RA impairs the antigen-presenting capacity of DCs, leading to down-regulation of pathogenic Th1 and Th17 inflammatory cell responses and reducing EAE severity.
© 2012 Blackwell Publishing Ltd.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antigen Presentation / drug effects
-
Antigens, CD / genetics
-
Antigens, CD / immunology
-
Antioxidants / pharmacology
-
Antioxidants / therapeutic use*
-
Cell Differentiation / drug effects
-
Dendritic Cells / drug effects*
-
Dendritic Cells / immunology
-
Dendritic Cells / pathology
-
Encephalomyelitis, Autoimmune, Experimental / chemically induced
-
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
-
Encephalomyelitis, Autoimmune, Experimental / immunology
-
Encephalomyelitis, Autoimmune, Experimental / pathology
-
Female
-
Gene Expression Regulation / drug effects
-
Histocompatibility Antigens Class II / genetics
-
Histocompatibility Antigens Class II / immunology
-
Immunization
-
Lymph Nodes / drug effects
-
Lymph Nodes / immunology
-
Lymph Nodes / pathology
-
Mice
-
Mice, Inbred C57BL
-
Monocytes / drug effects*
-
Monocytes / immunology
-
Monocytes / pathology
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
Signal Transduction / drug effects
-
Spinal Cord / drug effects
-
Spinal Cord / immunology
-
Spinal Cord / pathology
-
Spleen / drug effects
-
Spleen / immunology
-
Spleen / pathology
-
Th1 Cells / drug effects
-
Th1 Cells / immunology
-
Th1 Cells / pathology
-
Th17 Cells / drug effects
-
Th17 Cells / immunology
-
Th17 Cells / pathology
-
Tretinoin / pharmacology
-
Tretinoin / therapeutic use*
Substances
-
Antigens, CD
-
Antioxidants
-
Histocompatibility Antigens Class II
-
Myelin-Oligodendrocyte Glycoprotein
-
Peptide Fragments
-
myelin oligodendrocyte glycoprotein (35-55)
-
Tretinoin