Intestinal Specific Overexpression of Interleukin-7 Attenuates the Alternation of Intestinal Intraepithelial Lymphocytes After Total Parenteral Nutrition Administration

Abstract

Total parenteral nutrition (TPN), with the complete removal of enteral nutrition, results in marked changes in intestinal intraepithelial lymphocyte (IEL) function and phenotype. Previous work shows that TPN results in a loss of intestinal epithelial cell-derived interleukin-7 (IL-7), and this loss may play an important role in development of such TPN-associated IEL changes. To further understand this relation, we generated a transgenic mouse (IL-7), which overexpresses IL-7 specifically in intestinal epithelial cells. We hypothesized that this localized overexpression would attenuate many of the observed TPN-associated IEL changes. Our study showed that TPN administration led to significant changes in IEL phenotype, including a marked decline in the CD8alphabeta+, CD4+, and alphabeta-TCR+ populations. IEL basal proliferation decreased 1.7-fold compared with wild-type TPN mice. TPN administration in wild-type mice resulted in several changes in IEL-derived cytokine expression. IL-7 mice given TPN, however, maintained IEL proliferation, and sustained normal IEL numbers and phenotype. We conclude that specific intestinal IL-7 overexpression significantly attenuated many IEL changes in phenotype and function after TPN administration. These findings suggest a mechanism by which TPN results in observed IEL changes.