Interleukin-23 drives innate and T cell–mediated intestinal inflammation

By S. Hue, Philip P. Ahern, S. Buonocore, M. Kullberg, D. Cua, Brent S. McKenzie, F. Powrie, K. Maloy. Journal of Experimental Medicine, 2006

889 citations recorded by the source corpus.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract involving aberrant activation of innate and adaptive immune responses. We have used two complementary models of IBD to examine the roles of interleukin (IL)-12 family cytokines in bacterially induced intestinal inflammation. Our results clearly show that IL-23, but not IL-12, is essential for the induction of chronic intestinal inflammation mediated by innate or adaptive immune mechanisms. Depletion of IL-23 was associated with decreased proinflammatory responses in the intestine but had little impact on systemic T cell inflammatory responses. These results newly identify IL-23 as a driver of innate immune pathology in the intestine and suggest that selective targeting of IL-23 represents an attractive therapeutic approach in human IBD.

Subfields: Immunology, Pathology and Forensic Medicine

View Paper: https://www.semanticscholar.org/paper/e98c7ff022861d04df29a34b647cbf0b7b92ccef

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. R. Flavell
2. Dan R. Littman
3. D. Cua
4. K. Honda
5. J. Kolls
6. F. Powrie
7. J. O’Shea
8. C. Tato

In Pathology and Forensic Medicine

1. D. Cua
2. Y. Iwakura
3. J. Kolls
4. C. Tato
5. M. McGeachy
6. R. Flavell
7. F. Powrie
8. Dan R. Littman

Citations in the corpus

• A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses (2009, positive): “Stat3-driven T H 17 responses, characterized by production of IL-17A in mice and humans and driven by IL-23, are crucial in mucosal inflammatory responses in the lung and gut and are implicated in a number of autoimmune disorder”
• Interleukin 23 receptor is essential for terminal differentiation of effector T helper type 17 cells in vivo (2009, background): “One further factor that complicates the interpretation of results obtained with IL-23-deficient mice is that IL-23 may also have important proinflammatory effects on cells of the innate immune syste”
• Induction of intestinal Th17 cells by segmented filamentous bacteria (2009, background): “Do SFB Influence Th17 Cell-Mediated Inflammatory Disease? Th17 cells are recognized to have significant roles in multiple mouse models of autoimmune disease, and there is accumulating evidence that they likewise contribute to human autoimmune disease pathogenesis (Hue et al., 2006; Langrish et al., ”
• IL-6 programs TH-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways (2007, background): “The importance of IL-23 in inflammatory disease in both mice and humans is emphasized by findings of its inductive function in mouse colitis model”
• A protective function for interleukin 17A in T cell–mediated intestinal inflammation (2009, positive): “In mouse colitis studies using either adoptive transfer of CD45RB hi T cells or infection with helicobacter to induce IBD, investigators have documented expression of IL-23, IL-17 and IFN-γ in the inflamed colon tissu”
• Cytokine Networks in the Pathophysiology of Inflammatory Bowel Disease. (2019, background): “It led to observations that IL-23, as opposed to IL-12, is a major driver of chronic colitis (Hue et al., 2006; Uhlig et al., 2006; Yen et al., 2006).”
• Progressive loss of RORγt expression confers distinct functional fates to natural killer cell receptor-expressing RORγt+ innate lymphocytes (2010, positive): “…forms of autoimmunity have often been perceived to be exclusively caused by lymphocytes of the adaptive immune system, but recent evidence suggests that IL-23-responsive innate lymphoid cells may be sufficient to cause colitis in mice (Buonocore et al., 2010; Hue et al., 2006; Uhlig et al., 2006).”
• Immune adaptations that maintain homeostasis with the intestinal microbiota (2010, background): “The colitogenic T cells in these mice have T H 1 and T H 17 cell characteristics, and disease is attenuated if recipient mice lack the p19 subunit of IL-23 or are infused with T Reg cell”
• TGF-β and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell–mediated pathology (2007, background): “Whether these effects of IL-23 are on innate cells, as has been described in several colitis model”