Interleukin-7 administration alters intestinal intraepithelial lymphocyte phenotype and function in vivo

Abstract

Background Interleukin-7 (IL-7) plays a crucial role in controlling T-cell development and homeostasis. IL-7 knock out and IL-7 receptor knock out mice show distinct declines in absolute numbers of the intestinal intraepithelial lymphocytes (IEL). Therefore, we hypothesized that exogenous administration of IL-7 would alter IEL phenotype and function. Methods Adult C57BL/6J mice were treated with IL-7 or saline. Mice were euthanized at day 7. Cytokine and keratinocyte growth factor (KGF) expressions were measured with RT-PCR. IEL phenotype was studied with flow cytometry. Finally, to address the association of endogenous epithelial cell (EC)-derived IL-7 and IEL, confocal microscopy was used to observe co-localization of IL-7 to IEL subpopulations. Results IL-7 administration significantly increased IEL numbers. CD8αβ+ IEL increased 3.2-fold, CD8+CD44+ IEL increased 1.3-fold, and αβ-T-cell receptor (TCR)+ IEL increased 1.3-fold. IL-7 administration also significantly changed both αβ-TCR+ IEL- and γδ-TCR+ IEL-derived cytokine expressions. Interestingly, IL-7 administration also led to a significant increase in KGF expression. Confocal microscopy showed a high level of co-localization between the αβ-TCR+ IEL and EC-derived IL-7. γδ-TCR+ IEL showed a lower level, but still significant, co-localization. Conclusion IL-7 administration significantly affected IEL phenotype and function. The observed co-localization suggests that there is a close IEL–EC cross-communication mediated by EC-derived IL-7 expression.