title: Transgenic mice that overexpress human IL-15 in enterocytes recapitulate both B and T cell-mediated pathologic manifestations of celiac disease.
abstract: Celiac disease (CD) is a chronic immune-mediated intestinal inflammatory disorder afflicting genetically susceptible individuals triggered by the consumption of dietary cereals with high gluten content. As with many other organ-specific autoimmune diseases, the dominant tissue-destructive inflammation in CD is T cell-mediated. The proinflammatory cytokine IL-15 that is overexpressed in the intestinal epithelium of CD patients has emerged as a pivotal element that orchestrates intestinal inflammation and T cell-mediated autoimmune tissue destruction. Although no animal model exists that recapitulates the full spectrum of CD pathophysiology, we have previously reported that transgenic mice that overexpress human IL-15 in enterocytes (T3(b)-hlL-15 Tg) display many of the T cell-mediated pathologic features seen in CD. Extending these observations, we now report that T3(b)-hlL-15 Tg mice in addition to recapitulating T cell-mediated effects also display autoantibodies including those against tissue transglutaminase 2 and extensive lamina propria plasmacytosis, all of which are characteristic of CD, thereby reflecting the possibility that locally expressed IL-15 drives both T and B cell pathologic effects seen in CD. More importantly, these findings support the validity and utility of T3(b)-hlL-15 Tg mice as a reasonable model to investigate not only tissue-destructive pathologic processes in CD, but also to explore novel therapeutic modalities for the treatment of this disease.
authors.affiliation: Department of Allergy and Immunology, The Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Kazuko
authors.initials: K
authors.lastname: Takada
authors.forename: Masatomo
authors.initials: M
authors.lastname: Hirasawa
authors.forename: Liyanage P
authors.initials: LP
authors.lastname: Perera
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D002446:Celiac Disease / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement; D004195:Disease Models, Animal; D020895:Enterocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019204:GTP-Binding Proteins / Q000276:immunology; D006801:Humans; D007249:Inflammation; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D010950:Plasma Cells / Q000473:pathology*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D013601:T-Lymphocytes / Q000276:immunology; D019076:Transgenes / Q000235:genetics; D011503:Transglutaminases / Q000276:immunology
chemical_list: D001323:Autoantibodies; D019409:Interleukin-15; C000717608:TGM2 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins