Experimental autoimmune encephalomyelitis (EAE) is an animal model of
multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific
autoimmune disease. In the rat, susceptibility to development of these
diseases is shown to be strain-and age-dependent. In adult rats of distinct
strains, it correlates with splenic dendritic cell (DC) subset composition,
which also exhibit age-related changes. The aim of this study was to examine
influence of aging on: i) Albino Oxford (relatively resistant to EAE) and
Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic
conventional (OX62+) DC population in respect to its subset composition and
expression of mRNAs for proinflammatory and immunosuppressive cytokines. We
used 3month-old (young) and 26-month-old (aged) rats of AO and DA strain. The
rats were immunized for EAE with rat spinal cord homogenate in complete
Freund?s adjuvant and clinical course of the disease was followed. Fresh
OX62+DCs were examined for the expression of CD4 (using flow cytometry) and
genes encoding cytokines influencing DC activation/maturation (TNF-? and
IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS)
activated/matured DCs were examined for the expression of genes encoding
cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO
rats became more susceptible, whereas DA rats largely lose their
susceptibility to the induction of EAE. In AO rats aging shifted CD4+:CD4DC
ratio towards CD4-cells, producing large amount of proinflammatory cytokines,
whereas in DA rats CD4+:CD4-DC ratio remained stable with aging. In fresh DCs
from rats of both the strains the expression of TNF-? mRNA increased with
aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and
DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged
AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of
IL-23; crucial for sustained IL-17 production) and IL-1? (positive IL-17
regulator), whereas down-regulated the expression of IL-10 (negative IL-17
regulator) when compared with young strain-matched rats. In DA rats aging
incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the
opposing effects on the expression of mRNAs for IL-10 and IL-1? compared to
AO rats. Irrespective of the rat strain, aging did not influence mRNA
expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results
suggest role of changes in the expression of genes encoding proinflammatory
and immunosuppressive cytokines in development of age-related alterations in
rat susceptibility to EAE induction.
Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression
