Aiping M Zhao

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Critical role of IL-25 in nematode infection-induced alterations in intestinal function.

Aiping Zhao; Joseph F Urban; Rex Sun; Jennifer Stiltz; Motoko Morimoto; Luigi Notari; Kathleen B Madden; Zhonghan Yang; Viktoriya Grinchuk; Thirumalai R Ramalingam; et al. (Profiled Authors: Terez Shea-Donohue; Aiping M Zhao; Luigi Notari)

Department of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA. azhao@mbrc.umaryland.edu
Journal of immunology (Baltimore, Md. : 1950) 2010;185(11):6921-9.

IL-25 (IL-17E) is a member of the IL-17 cytokine family. IL-25-deficient mice exhibit impaired Th2 immunity against nematode infection, implicating IL-25 as a key component in mucosal immunity. The sources of IL-25 and mechanisms responsible for the induction of Th2 immunity by IL-25 in the gastrointestinal tract remain poorly understood. There is also little information on the regulation of IL-25 during inflammation or its role in gut function. In the current study, we investigated the regulation of IL-25 during Nippostrongylus brasiliensis infection and the contribution of IL-25 to the infection-induced alterations in intestinal function. We found that epithelial cells, but not immune cells, are the major source of IL-25 in the small intestine. N. brasiliensis infection-induced upregulation of IL-25 depends upon IL-13 activation of STAT6. IL-25(-/-) mice had diminished intestinal smooth muscle and epithelial responses to N. brasiliensis infection that were associated with an impaired Th2 protective immunity. Exogenous IL-25 induced characteristic changes similar to those after nematode infection but was unable to restore the impaired host immunity against N. brasiliensis infection in IL-13(-/-) mice. These data show that IL-25 plays a critical role in nematode infection-induced alterations in intestinal function that are important for host protective immunity, and IL-13 is the major downstream Th2 cytokine responsible for the IL-25 effects.

1 Originating Grant

• 1.

  ZHAO, AIPING

  Novel Cytokine Regulation of Gut Function and Inflammation

  1 June 2009 - 31 March 2014

  NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES

Scientific Context

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