Strain difference in susceptibility to experimental autoimmune encephalomyelitis between Albino Oxford and Dark Agouti rats correlates with disparity in production of IL-17, but not nitric oxide

Abstract

Albino Oxford (AO) rats, unlike Dark Agouti (DA) rats are resistant to the induction of experimental autoimmune encephalomyelitis (EAE). The reason for the resistance could be some restraining mechanism preventing auto-aggressive cell activation at the level of draining lymph nodes (DLN) during the induction phase of the disease. Such a mechanism could be anti-proliferative action of nitric oxide (NO), which has already been shown of importance for the resistance of several rat strains to the induction of the disease. Importantly, number of AO DLN cells (DLNC) is markedly lower and with lower proliferative response to myelin basic protein (MBP) ex vivo in comparison to DA DLNC in the inductive phase of EAE, thus implying that in AO rats DLNC do not proliferate as extensively as in DA rats. We show that AO rats do not produce larger quantities of NO than DA rats after immunization. Further, DLNC of immunized AO rats have significantly lower mRNA expression and synthesis of interferon (IFN)-gamma and interleukin (IL)-17 compared to DLNC of DA rats. Collectively, these results suggest that there is a substantial difference between EAE-resistant AO rats and EAE-prone DA rats in the initiation of autoimmune response. This difference seems to be independent of anti-proliferative actions of NO, but correlates with impaired IL-17 production in AO rats.

Astrocytes stimulate interleukin‐17 and interferon‐γ production in vitro

“…More recently, a distinct population of Th17 IL-17-secreting cells has been increasingly gaining recognition for its importance in the pathology of CNS autoimmunity (Langrish et al, 2005). We have recently reported that both IL-17 and IFN-g gene expression and cytokine production by DLNC are much higher in EAE-prone DA rats than in EAE-resistant AO rats (Miljkovic et al, 2006), and here we show a clear dominance of CNS-infiltrating cells to DLNC in their ability to express both of these cytokines. It has previously been reported that cells infiltrating CNS at the peak of clinical EAE produced severalfold higher amounts of IFN-g compared with draining lymph node and spleen cells (Xiao et al, 1998;Hoffstetter et al, 2006).…”

Neuroprotection without Immunomodulation Is Not Sufficient to Reduce First Relapse Severity in Experimental Autoimmune Encephalomyelitis

“…The pronounced decrease in CNS T cells and the sustained T H 1 response following treatment with high doses of R(+)WIN55,212-2 led us to explore the T H 17 cell lineage since it has been linked to various autoimmune diseases including MS [59][60][61] . We found a dose-dependent decrease in T H 17-positive cells that mirrored EAE severity ( fig.…”

Betulinic acid regulates generation of neuroinflammatory mediators responsible for tissue destruction in multiple sclerosis in vitro

“…Both IL-17 and IFN-γ are continuously produced by DLNC and SCC in Dark Agouti rats immunized to develop EAE [16] . Furthermore, low production of IL-17 and IFN-γ in DLNC, as well as low production of the cytokines that induce IL-17 and IFN-γ generation (including IL-6, IL-12, and IL-23) in DLNC, have been associated with the resistance of Albino Oxford rats to EAE induction [17,18] . Regarding MS, it has been shown that IL-17 is elevated in immune cells within the CNS and at the periphery and that it contributes to the pathogenesis of the disease, eg through distortion of the blood-brain-barrier [19][20][21] .…”