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

By C. Langrish, Yi Chen, W. Blumenschein, J. Mattson, Beth Basham, J. Sedgwick, T. Mcclanahan, R. Kastelein, D. Cua. 2005

4,408 citations recorded by the source corpus.

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-γ–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.

Subfields: Immunology

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In Immunology

1. D. Cua
2. W. E. Paul
3. Dan R. Littman
4. A. Jetten
5. Jinfang Zhu
6. C. Dong
7. R. Flavell
8. TA Wynn

Citations in the corpus

• Expanding the effector CD4 T-cell repertoire: the Th17 lineage. (2006, methodology): “Especially in view ofthe limited effect of IL-23 to promote the development of IL-17 effectors from nai¨ve CD4 precursors [14, 23 ], it is not surprising that models of IL-17 effector differentiation have been linked to the Th1 pathway.”
• The development of inflammatory TH-17 cells requires interferon-regulatory factor 4 (2007, background): “Evidence has clarified that T H -17 cells, rather than T H 1 cells, are important in autoimmune inflammatory conditions such as experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosi”
• Expanded Double Negative T Cells in Patients with Systemic Lupus Erythematosus Produce IL-17 and Infiltrate the Kidneys (2008, background): “matory responses by virtue of producing IL-17A and IL-17F (11).”
• MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development (2010, background): “Th17 cell development is driven by cytokines produced primarily by cells of the innate immune system, including transforming growth factor-b (TGF-b), interleukin-6 (IL-6), IL-23, and IL-1 (Bettelli et al., 2006; Langrish et al., 2005; Veldhoen et al., 2006).”
• Cutting Edge: An In Vivo Requirement for STAT3 Signaling in TH17 Development and TH17-Dependent Autoimmunity1 (2007, background): “Considerable data show that the induction of EAE is critically dependent on TH17 T cell differentiation (8, 9).”
• Exploring the full spectrum of macrophage activation (2008, background): “For example, IL-1 , IL-6 and IL-23 are produced by classically activated macrophages and have been associated with the development and expansion of T H 17 cell”
• IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2–dependent mechanisms with implications for psoriasis pathogenesis (2006, background): “IL-23 is a potent regulator of memory T cell development and/or expansion that is skewed to IL-17A secretion (36), and IL-23 has been implicated as a key disease driver in autoimmune disease models (13, 23).”
• Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. (2008, background): “The principle findings were as follows: (1) the GI tract is enriched in Th17 cells compared with PB in healthy patients; (2) CD4 T cells in blood of HIV-infected patients are skewed away from a Th17 phenotype toward a monofunctional Th1 phenotype with cellular maturation; (3) PB Th17 cells are infec”
• Interleukin 23 receptor is essential for terminal differentiation of effector T helper type 17 cells in vivo (2009, background): “T H -17 cells were initially shown to be a chief pathogenic cell type in models of autoimmunity, including experimental autoimmune encephalomyelitis (EAE”
• MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis (2009, background): “Mice with fewer T H -17 cells are less susceptible to experimental autoimmune encephalomyelitis (EAE”