The correlation between severity of paraparesis and reduced density of resident antigen-presenting cells implicates an unknown role for the spinal perivascular macrophages in experimental autoimmune encephalomyelitis in rats

2003 ◽  
Vol 142 (1-2) ◽  
pp. 31-46 ◽  
Author(s):  
Dennis N Schmitz ◽  
Nils Hofmann ◽  
Toma L Tomov ◽  
Adam D Kovac ◽  
Wolfram F Neiss ◽  
...  
Keyword(s):  
Experimental Autoimmune Encephalomyelitis ◽  
Antigen Presenting Cells ◽  
Autoimmune Encephalomyelitis ◽  
Perivascular Macrophages ◽  
Reduced Density ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Pituitary adenylate cyclase-activating polypeptide (PACAP) ameliorates experimental autoimmune encephalomyelitis by suppressing the functions of antigen presenting cells

2004 ◽  
Vol 10 (6) ◽  
pp. 651-659 ◽  
Author(s):  
Hideki Kato ◽  
Atsushi Ito ◽  
Jun Kawanokuchi ◽  
Shijie Jin ◽  
Tetsuya Mizuno ◽  
...  
Keyword(s):  
T Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Adenylate Cyclase ◽  
Ex Vivo ◽  
Antigen Presenting Cells ◽  
Significant Inhibition ◽  
Autoimmune Encephalomyelitis ◽  
Pituitary Adenylate Cyclase ◽  
Antigen Presenting ◽  
Experimental Autoimmune

Pituitary adenylate cyclase-activating polypeptide (PACAP), a 38-amino acid neuropeptide belonging to the secretin-glucagon-vasoactive intestinal peptide (VIP) family, performs a variety of functions in both the nervous and immune systems. In this study, we examined the effects of PACAP on experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. When administrated intraperitoneally every other day after immunization with myelin oligodendrocyte glycoprotein (MOG) peptide 35 -55, PACAP ameliorated both the clinical and pathological manifestations of EAE. Ex vivo examination revealed a significant inhibition of MOG35 55-specific Th1 response in mice treated with PACAP.In vitro analysis revealed that PACAP suppressed the production of inflammatory cytokines, including TNF-a, IL-1b, and IL-12, and expression of the costimulatory factor B7-2 on macrophage and microglia, which may function as antigen presenting cells (APC) in the CNS. While PACAP suppressed the differentiation of MOG35 55-specific T cells into Th1 effectors upon restimulation with MOG35 55-expressing APC, it did not affect interferon (IFN)-g production by MOG35 55-specific T cells stimulated with anti-CD3 and anti-CD28. These observations suggested that PACAP suppressed induction of EAE primarily via suppression of APC function and inflammatory cytokine production. PACAP may be useful in the future treatment of Th1-mediated autoimmune diseases, such as multiple sclerosis.

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