Intestinal intraepithelial lymphocyte gamma delta-T cell-derived keratinocyte growth factor modulates epithelial growth in the mouse

• Published in: The Journal of immunology (1950) 2004-04, Vol.172 (7), p.4151-4158
• Main Authors: Yang, Hua, Antony, Paul A, Wildhaber, Barbara E, Teitelbaum, Daniel H
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - biosynthesis; Adjuvants, Immunologic - physiology; Animals; Atrophy; Cell Division - genetics; Cell Division - immunology; Fibroblast Growth Factor 7; Fibroblast Growth Factors - biosynthesis; Fibroblast Growth Factors - physiology; Hypertrophy; Intestinal Mucosa - cytology; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Jejunum - immunology; Jejunum - metabolism; Jejunum - pathology; Jejunum - surgery; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microdissection - methods; Microvilli - pathology; Parenteral Nutrition, Total; Receptors, Antigen, T-Cell, gamma-delta - biosynthesis; Receptors, Antigen, T-Cell, gamma-delta - deficiency; Receptors, Antigen, T-Cell, gamma-delta - genetics; Short Bowel Syndrome - genetics; Short Bowel Syndrome - immunology; Short Bowel Syndrome - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767
• DOI: 10.4049/jimmunol.172.7.4151

Keratinocyte growth factor (KGF) promotes intestinal epithelial growth. To understand the relevance of intraepithelial lymphocyte (IEL)-derived KGF expression on epithelial growth, we used a mouse model of villus atrophy by the administration of total parenteral nutrition, and a model of villus hypertrophy by the creation of a short bowel syndrome. KGF expression was confined to gammadelta-TCR(+) IELs. IEL-derived KGF expression was highest in the crypts, somewhat less in the lower portion of villi, and markedly lower in the upper portion of villi. Total parenteral nutrition administration was associated with a down-regulation of IEL-derived KGF expression, and short bowel syndrome was associated with an up-regulation of IEL-derived KGF expression. In the absence of gammadelta-TCR(+) IEL, using gammadelta(-/-) mice, intestinal epithelial cell proliferation decreased in control, and in both mucosal atrophy (22% decline) and mucosal hypertrophy (14%) models. These results show that KGF from IELs is an important factor for maintenance of intestinal epithelial cell proliferation and villus growth.