IL-23 drives a pathogenic T cell population that induces autoimmune inflammation

• Published in: The Journal of experimental medicine 2005-01, Vol.201 (2), p.233-240
• Main Authors: Langrish, Claire L, Chen, Yi, Blumenschein, Wendy M, Mattson, Jeanine, Basham, Beth, Sedgwick, Jonathan D, McClanahan, Terrill, Kastelein, Robert A, Cua, Daniel J
• Format: Article
• Language: English
• Subjects: Animals; Autoimmunity - immunology; Autoimmunity - physiology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - pathology; Central Nervous System - cytology; Central Nervous System - metabolism; Cytokines - metabolism; Encephalomyelitis, Autoimmune, Experimental - immunology; Encephalomyelitis, Autoimmune, Experimental - metabolism; Gene Expression - physiology; Gene Expression Profiling; Inflammation - immunology; Inflammation - metabolism; Interleukin-12 - metabolism; Interleukin-17 - metabolism; Interleukin-23; Interleukin-23 Subunit p19; Interleukins - metabolism; Mice; Time Factors
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.20041257

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.