Interleukin-7 administration alters intestinal intraepithelial lymphocyte phenotype and function in vivo.
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. CD8alphabeta+ IEL increased 3.2-fold, CD8+CD44+ IEL increased 1.3-fold, and alphabeta-T-cell receptor (TCR)+ IEL increased 1.3-fold. IL-7 administration also significantly changed both alphabeta-TCR+ IEL- and gammadelta-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 alphabeta-TCR+ IEL and EC-derived IL-7. gammadelta-TCR+ IEL showed a lower level, but still significant, co-localization.


CONCLUSIONS
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.
Yang
Hua
H
Section of Pediatric Surgery, Department of Surgery, The University of Michigan Medical School, Ann Arbor, 48109, USA.
Spencer
Ariel U
AU
Teitelbaum
Daniel H
DH
D000818:Animals; D002450:Cell Communication; D002453:Cell Cycle / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015851:Interleukin-7 / Q000494:pharmacology* / Q000502:physiology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology
D016207:Cytokines; D015851:Interleukin-7; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta