Library Subscription: Guest
Begell Digital Portal Begell Digital Library eBooks Journals References & Proceedings Research Collections
Critical Reviews™ in Immunology
IF: 1.352 5-Year IF: 3.347 SJR: 0.657 SNIP: 0.55 CiteScore™: 2.19

ISSN Print: 1040-8401
ISSN Online: 2162-6472

Critical Reviews™ in Immunology

DOI: 10.1615/CritRevImmunol.v24.i2.20
18 pages

Role of the IL-12/IL-23 System in the Regulation of T-Cell Responses in Central Nervous System Inflammatory Demyelination

Bruno Gran
Department of Neurology, Thomas Jefferson University, 300 Jefferson Hospital for Neuroscience, 900 Walnut Street, Philadelphia, PA 19107
Guang-Xian Zhang
Department of Neurology, Thomas Jefferson University, 300 Jefferson Hospital for Neuroscience, 900 Walnut Street, Philadelphia, PA 19107
Abdolmohamad Rostami
Department of Neurology, Thomas Jefferson University, 300 Jefferson Hospital for Neuroscience, 900 Walnut Street, Philadelphia, PA 19107

ABSTRACT

Interleukin-12 (IL-12) has long been considered essential in T-cell-mediated autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). This is based on the strong capacity of IL-12 to induce T-cell activation and Th1 differentiation. However, recent data have shown that the perceived central role of IL-12 in CNS inflammatory demyelination is actually due to IL-23, a closely related cytokine sharing the p40 subunit and the β1 receptor chain with IL-12. There appear to be three different aspects of IL-12 involvement in EAE: (1) disease-promoting effects of exogenous IL-12, particularly in relapsing—remitting EAE and adoptive transfer EAE; (2) lack of IL-12 requirement in EAE pathogenesis, as indicated by studies in knockout mice; and (3) immunoregulatory effects of IL-12. Together, these observations make IL-12 a less attractive target for therapeutic intervention in MS. IL-23 neutralization may be a better candidate for therapeutic intervention, and it remains to be established whether blocking IL-23 with antibodies in adult mice will have the same effects as knocking out the IL-23p19 gene. Current clinical trials of neutralizing anti— IL-12 antibodies in other immune-mediated diseases target the p40 subunit, thereby neutralizing both IL-12 and IL-23. Thus, new experimental data are expected to have important implications for therapy of human diseases.


Articles with similar content:

T Lymphocytes and Their Cytokines in Human Immunodeficiency Virus (HIV) Infection: Implications for Associated Neoplasias
Critical Reviews™ in Oncogenesis, Vol.6, 1995, issue 3-6
Christian Jassoy, Bruce D. Walker
The Immunomodulating Effects of Ganoderma lucidum (Curt.: Fr.) P. Karst. (Ling Zhi, Reishi Mushroom) (Aphyllophoromycetideae)
International Journal of Medicinal Mushrooms, Vol.4, 2002, issue 1
Yihuai Gao, Shufeng Zhou
Immunopathogenesis of Colitis-Associated Cancer in an Animal Model
Critical Reviews™ in Eukaryotic Gene Expression, Vol.25, 2015, issue 3
Chuan-Xing Xiao, Bayasi Guleng, Jun-Lin Zhao
Human TCR as Antigen: Homologies and Potentially Cross-Reactive HLA-DR2-Restricted Epitopes Within the AV and BV CDR2 Loops
Critical Reviews™ in Immunology, Vol.20, 2000, issue 1
Arthur A. Vandenbark, Halina Offner, Abigail Buenafe, David Barnes, Gregory G. Burrows, Sandra Law, Yuan K. Chou, Tom Finn, Nicole Culbertson
Function and Regulation of Retinoic Acid-Inducible Gene-I
Critical Reviews™ in Immunology, Vol.30, 2010, issue 6
Diana M. Stafforini, Tomoh Matsumiya