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 - PubMed (original) (raw)
Comparative Study
. 2002 Dec 15;169(12):7104-10.
doi: 10.4049/jimmunol.169.12.7104.
Affiliations
- PMID: 12471147
- DOI: 10.4049/jimmunol.169.12.7104
Comparative Study
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
Bruno Gran et al. J Immunol. 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.
Similar articles
- Role of IL-12 receptor beta 1 in regulation of T cell response by APC in experimental autoimmune encephalomyelitis.
Zhang GX, Yu S, Gran B, Li J, Siglienti I, Chen X, Calida D, Ventura E, Kamoun M, Rostami A. Zhang GX, et al. J Immunol. 2003 Nov 1;171(9):4485-92. doi: 10.4049/jimmunol.171.9.4485. J Immunol. 2003. PMID: 14568921 - Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12.
Becher B, Durell BG, Noelle RJ. Becher B, et al. J Clin Invest. 2002 Aug;110(4):493-7. doi: 10.1172/JCI15751. J Clin Invest. 2002. PMID: 12189243 Free PMC article. - Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination.
Rostami A, Ciric B. Rostami A, et al. J Neurol Sci. 2013 Oct 15;333(1-2):76-87. doi: 10.1016/j.jns.2013.03.002. Epub 2013 Apr 8. J Neurol Sci. 2013. PMID: 23578791 Free PMC article. Review. - The power of combinatorial immunology: IL-12 and IL-12-related dimeric cytokines in infectious diseases.
Hölscher C. Hölscher C. Med Microbiol Immunol. 2004 Feb;193(1):1-17. doi: 10.1007/s00430-003-0186-x. Epub 2003 Jun 27. Med Microbiol Immunol. 2004. PMID: 12836019 Review.
Cited by
- An IL-23-STAT4 pathway is required for the proinflammatory function of classical dendritic cells during CNS inflammation.
Alakhras NS, Zhang W, Barros N, Sharma A, Ropa J, Priya R, Yang XF, Kaplan MH. Alakhras NS, et al. Proc Natl Acad Sci U S A. 2024 Aug 6;121(32):e2400153121. doi: 10.1073/pnas.2400153121. Epub 2024 Aug 1. Proc Natl Acad Sci U S A. 2024. PMID: 39088391 - Correlation of Visual System Biomarkers With Motor Deficits in Experimental Autoimmune Encephalomyelitis-Optic Neuritis.
Elwood BW, Godwin CR, Anders JJ, Kardon RH, Gramlich OW. Elwood BW, et al. Transl Vis Sci Technol. 2024 Aug 1;13(8):1. doi: 10.1167/tvst.13.8.1. Transl Vis Sci Technol. 2024. PMID: 39087931 Free PMC article. - The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.
Amoriello R, Memo C, Ballerini L, Ballerini C. Amoriello R, et al. Mol Brain. 2024 Jan 23;17(1):4. doi: 10.1186/s13041-024-01077-7. Mol Brain. 2024. PMID: 38263055 Free PMC article. Review. - IL-12 sensing in neurons induces neuroprotective CNS tissue adaptation and attenuates neuroinflammation in mice.
Andreadou M, Ingelfinger F, De Feo D, Cramer TLM, Tuzlak S, Friebel E, Schreiner B, Eede P, Schneeberger S, Geesdorf M, Ridder F, Welsh CA, Power L, Kirschenbaum D, Tyagarajan SK, Greter M, Heppner FL, Mundt S, Becher B. Andreadou M, et al. Nat Neurosci. 2023 Oct;26(10):1701-1712. doi: 10.1038/s41593-023-01435-z. Epub 2023 Sep 25. Nat Neurosci. 2023. PMID: 37749256 Free PMC article. - T cells in health and disease.
Sun L, Su Y, Jiao A, Wang X, Zhang B. Sun L, et al. Signal Transduct Target Ther. 2023 Jun 19;8(1):235. doi: 10.1038/s41392-023-01471-y. Signal Transduct Target Ther. 2023. PMID: 37332039 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials