IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination.
Publication/Presentation Date
12-15-2002
Abstract
Experimental autoimmune encephalomyelitis (EAE) serves as a model for multiple sclerosis and is considered a CD4(+), Th1 cell-mediated autoimmune disease. IL-12 is a heterodimeric cytokine, composed of a p40 and a p35 subunit, which is thought to play an important role in the development of Th1 cells and can exacerbate EAE. We induced EAE with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (MOG(35-55)) in C57BL/6 mice and found that while IL-12p40-deficient (-/-) mice are resistant to EAE, IL-12p35(-/-) mice are susceptible. Typical spinal cord mononuclear cell infiltration and demyelination were observed in wild-type and IL-12p35(-/-) mice, whereas IL-12p40(-/-) mice had normal spinal cords. A Th1-type response to MOG(35-55) was observed in the draining lymph node and the spleen of wild-type mice. A weaker MOG(35-55)-specific Th1 response was observed in IL-12p35(-/-) mice, with lower production of IFN-gamma. By contrast, a Th2-type response to MOG(35-55) correlated with disease resistance in IL-12p40(-/-) mice. Production of TNF-alpha by microglia, CNS-infiltrating macrophages, and CD4(+) T cells was detected in wild-type and IL-12p35(-/-), but not in IL-12p40(-/-), mice. In addition, NO production was higher in IL-12p35(-/-) and wild-type mice than in IL-12p40(-/-) mice. These data demonstrate a redundancy of the IL-12 system in the induction of EAE and suggest that p40-related heterodimers, such as the recently cloned IL-23 (p40p19), may play an important role in disease pathogenesis.
Volume
169
Issue
12
First Page
7104
Last Page
7110
ISSN
0022-1767
Published In/Presented At
Gran, B., Zhang, G. X., Yu, S., Li, J., Chen, X. H., Ventura, E. S., Kamoun, M., & Rostami, A. (2002). IL-12p35-deficient mice are susceptible to experimental autoimmune encephalomyelitis: evidence for redundancy in the IL-12 system in the induction of central nervous system autoimmune demyelination. Journal of immunology (Baltimore, Md. : 1950), 169(12), 7104–7110. https://doi.org/10.4049/jimmunol.169.12.7104
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
12471147
Department(s)
Administration and Leadership
Document Type
Article