Intravenous tolerance effectively overcomes enhanced pro-inflammatory responses and experimental autoimmune encephalomyelitis severity in the absence of IL-12 receptor signaling.
Publication/Presentation Date
6-15-2012
Abstract
Intravenous (i.v.) administration of autoantigen effectively induces Ag-specific tolerance against experimental autoimmune encephalomyelitis (EAE). We and others have shown enhanced EAE severity in mice lacking IL-12 or its receptor, strongly suggesting an immunoregulatory effect of IL-12 signaling. To examine the role of IL-12 responsiveness in autoantigen-induced tolerance in EAE, we administered autoantigen i.v. in two distinct treatment regimes to wildtype and IL-12Rβ2(-/-) mice, immunized to develop EAE. Administration at the induction phase suppressed EAE in wildtype and IL-12Rβ2(-/-) mice however the effect was somewhat less potent in the absence of IL-12Rβ2. Expression of pro-inflammatory cytokines such as IFN-γ, IL-17 and IL-2, was inhibited in wild-type tolerized mice but less so in IL-12Rβ2(-/-) mice. I.v. antigen was also effective in suppressing disease in both genotypes when given during the clinical phase of disease with similar CNS inflammation, demyelination and peripheral inflammatory cytokine profiles observed in both genotypes. There was however a mild impact of a lack of IL-12 signaling on Treg induction during tolerance induction compared to WT mice in this treatment regime. These findings show that the enhanced severity of EAE that occurs in the absence of IL-12 signaling can be effectively overcome by i.v. autoantigen, indicating that this therapeutic effect is not primarily mediated by IL-12 and that i.v. tolerance could be a powerful approach in suppressing severe and aggressive MS.
Volume
247
Issue
1-2
First Page
32
Last Page
37
ISSN
1872-8421
Published In/Presented At
Fitzgerald, D. C., Zhang, G. X., Yu, S., Cullimore, M. L., Zhao, Z., & Rostami, A. (2012). Intravenous tolerance effectively overcomes enhanced pro-inflammatory responses and experimental autoimmune encephalomyelitis severity in the absence of IL-12 receptor signaling. Journal of neuroimmunology, 247(1-2), 32–37. https://doi.org/10.1016/j.jneuroim.2012.03.021
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
22522341
Department(s)
Administration and Leadership
Document Type
Article