Intraepithelial NK cell-derived IL-13 induces intestinal pathology associated with nematode infection.
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.
McDermott
Jacqueline R
JR
Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
Humphreys
Neil E
NE
Forman
Simon P
SP
Donaldson
Debra D
DD
Grencis
Richard K
RK
D000818:Animals; D018793:Interleukin-13 / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000502:physiology; D007413:Intestinal Mucosa / Q000276:immunology*; D007422:Intestines / Q000473:pathology*; D007694:Killer Cells, Natural / Q000276:immunology*; D017493:Leukocyte Common Antigens / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D037121:Plant Lectins / Q000032:analysis; D018123:Receptors, Interleukin / Q000502:physiology; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000502:physiology; D017160:Trichinella spiralis; D014235:Trichinellosis / Q000276:immunology / Q000473:pathology*
C508183:Il13ra1 protein, mouse; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D037121:Plant Lectins; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; C036850:Ulex europaeus lectins; D015847:Interleukin-4; D017493:Leukocyte Common Antigens