Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• The Journal of experimental medicine, 2006-04, Vol.203 (4), p.843-849

Ort / Verlag

United States: The Rockefeller University Press

Erscheinungsjahr

2006

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.