Transgenic Mice that Overexpress Human IL-15 in Enterocytes Recapitulate Both B and T Cell-Mediated Pathologic Manifestations of Celiac Disease

• Published in: Journal of clinical immunology 2011-12, Vol.31 (6), p.1038-1044
• Main Authors: Yokoyama, Seiji, Takada, Kazuko, Hirasawa, Masatomo, Perera, Liyanage P., Hiroi, Takachika
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Autoantibodies; Autoantibodies - immunology; Autoantibodies - metabolism; Autoimmune diseases; B-Lymphocytes - immunology; Biomedical and Life Sciences; Biomedicine; Celiac disease; Celiac Disease - genetics; Celiac Disease - immunology; Cell Movement; Cereals; Disease Models, Animal; Enterocytes; Enterocytes - immunology; Enterocytes - metabolism; Enterocytes - pathology; Epithelium; Gluten; GTP-Binding Proteins - immunology; Humans; Immunology; Infectious Diseases; Inflammation; Inflammatory diseases; Interleukin 15; Interleukin-15 - genetics; Interleukin-15 - immunology; Interleukin-15 - metabolism; Internal Medicine; Intestinal Mucosa - pathology; Intestine; lamina propria; Lymphocyte Activation; Lymphocytes B; Medical Microbiology; Mice; Mice, Transgenic; Plasma Cells - pathology; Plasmacytosis; T-Lymphocytes - immunology; Transgenes - genetics; Transgenic mice; Transglutaminase 2; Transglutaminases - immunology
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-011-9586-7

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.