Intraepithelial NK cell-derived IL-13 induces intestinal pathology associated with nematode infection.

Abstract

IL-13 is a Th2-derived cytokine associated with pathological changes in asthma and ulcerative colitis. Moreover, it plays a major role in the control of gut nematode infection and associated immunopathology. The current paradigm is that these effects are due to T cell-derived IL-13. We show in this study that an innate source of IL-13, the intraepithelial NK cell, is responsible for the disruption of intestinal tissue architecture and induction of goblet cell hyperplasia that characterizes infection with the intestinal helminth Trichinella spiralis. IL-13 or IL-4Ralpha (but not IL-4) null mice failed to induce intestinal pathology. Unexpectedly, SCID and athymic mice developed the same pathology found in immunocompetent mice following infection. Moreover, immunodeficient mice expressed IL-13 in the intestine, and abnormal mucosal pathology was reduced by in vivo administration of a soluble IL-13 antagonist. IL-13 expression was induced in non-T intraepithelial CD3- NK cells. Epithelial cells expressed the IL-13 signaling receptor, IL-13Ralpha1, and after infection, IL-4Ralpha. Furthermore, the soluble IL-13 decoy receptor IL-13Ralpha2, which regulates IL-13 responses, was also induced upon infection. These data provide the first evidence that intestinal tissue restructuring during helminth infection is an innate event dependent on IL-13 production by NK cells resident in the epithelium of the intestine.

• Authors: Jacqueline R McDermott, Neil E Humphreys, Simon P Forman, Debra D Donaldson, Richard K Grencis
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 175 Issue 5 Pg. 3207-13 (Sep 01 2005) ISSN: 0022-1767 [Print] United States
• PMID: 16116211 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Il13ra1 protein, mouse
• Interleukin-13
• Interleukin-13 Receptor alpha1 Subunit
• Plant Lectins
• Receptors, Interleukin
• Receptors, Interleukin-13
• Receptors, Interleukin-4
• Ulex europaeus lectins
• Interleukin-4
• Leukocyte Common Antigens

Topics

• Animals
• Interleukin-13 (physiology)
• Interleukin-13 Receptor alpha1 Subunit
• Interleukin-4 (physiology)
• Intestinal Mucosa (immunology)
• Intestines (pathology)
• Killer Cells, Natural (immunology)
• Leukocyte Common Antigens (analysis)
• Mice
• Mice, Inbred BALB C
• Mice, SCID
• Plant Lectins (analysis)
• Receptors, Interleukin (physiology)
• Receptors, Interleukin-13
• Receptors, Interleukin-4 (physiology)
• Trichinella spiralis
• Trichinellosis (immunology, pathology)