Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract

• Published in: The Journal of experimental medicine Vol. 203; no. 4; pp. 843 - 849
• Main Authors: Owyang, Alexander M, Zaph, Colby, Wilson, Emma H, Guild, Katherine J, McClanahan, Terrill, Miller, Hugh R P, Cua, Daniel J, Goldschmidt, Michael, Hunter, Christopher A, Kastelein, Robert A, Artis, David
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 17-04-2006
• Subjects: Animals; Brief Definitive Reports; Cell Differentiation - immunology; Cells, Cultured; Chronic Disease; Cytokines - classification; Cytokines - physiology; Gastrointestinal Tract - immunology; Gastrointestinal Tract - parasitology; Gastrointestinal Tract - pathology; Inflammation - immunology; Inflammation - parasitology; Inflammation - pathology; Interleukins - genetics; Interleukins - physiology; Interleukins - therapeutic use; Mice; Mice, Inbred AKR; Mice, Inbred C57BL; Mice, Knockout; Mice, SCID; Recombinant Proteins - genetics; Recombinant Proteins - therapeutic use; Th1 Cells - cytology; Th1 Cells - immunology; Trichuriasis - drug therapy; Trichuriasis - immunology; Trichuris; Trichuris - immunology
• ISSN: 0022-1007; 1540-9538; 1892-1007
• DOI: 10.1084/jem.20051496

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25-deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25(-/-) mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-gamma and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract.