IL-23 drives a pathogenic T cell population that induces autoimmune inflammation.
Interleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12. IL-12 is important for the development of T helper (Th)1 cells that are essential for host defense and tumor suppression. In contrast, IL-23 does not promote the development of interferon-gamma-producing Th1 cells, but is one of the essential factors required for the expansion of a pathogenic CD4(+) T cell population, which is characterized by the production of IL-17, IL-17F, IL-6, and tumor necrosis factor. Gene expression analysis of IL-23-driven autoreactive T cells identified a unique expression pattern of proinflammatory cytokines and other novel factors, distinguishing them from IL-12-driven T cells. Using passive transfer studies, we confirm that these IL-23-dependent CD4(+) T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.
Langrish
Claire L
CL
Discovery Research, DNAX Research Inc., Palo Alto, CA 94304, USA.
Chen
Yi
Y
Blumenschein
Wendy M
WM
Mattson
Jeanine
J
Basham
Beth
B
Sedgwick
Jonathan D
JD
McClanahan
Terrill
T
Kastelein
Robert A
RA
Cua
Daniel J
DJ
D000818:Animals; D015551:Autoimmunity / Q000276:immunology* / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D020869:Gene Expression Profiling; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000378:metabolism*; D051379:Mice; D013997:Time Factors
D016207:Cytokines; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D018664:Interleukin-12