Pathophysiology of interleukin-23 in experimental autoimmune encephalomyelitis.
Interleukin-23 (IL-23) is a heterodimeric cytokine that is composed of a p40 subunit, shared with the closely related cytokine IL-12, and a smaller IL-23p19 subunit. It belongs to a family of heterodimeric cytokines that also includes IL-12 and IL-27. Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease that serves as a model for multiple sclerosis, an inflammatory demyelinating disease of the central nervous system that is a frequent cause of disability in young adults. EAE is thought to be initiated by CD4+ T cells. The production of interferon-gamma and tumor necrosis factor-alpha (T helper 1 [Th1] phenotype) was considered a marker for the ability of such cells to induce disease. Consistent with this view, IL-12, a cytokine that induces the differentiation of Th1 cells, was considered essential for EAE susceptibility. However, it is now clear that IL-23 rather than IL-12 is required for EAE susceptibility. IL-23 induces a population of IL-17-producing cells that is more critically involved in EAE pathogenesis than Th1 cells. Here, we review the role of the IL-23 system in the pathophysiology of EAE.
Touil
Tarik
T
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Fitzgerald
Denise
D
Zhang
Guang-Xian
GX
Rostami
A M
AM
Gran
Bruno
B
D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000209:etiology* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000502:physiology*; D051379:Mice; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D018123:Receptors, Interleukin / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology
D016207:Cytokines; C508840:IL23A protein, human; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018123:Receptors, Interleukin