Journal
CELL AND TISSUE RESEARCH
Volume 361, Issue 3, Pages 799-810Publisher
SPRINGER
DOI: 10.1007/s00441-015-2151-6
Keywords
Intraepithelial lymphocyte (IEL); DNA fragmentation; Immunohistology; Small intestine; Mouse (Balb/c)
Categories
Funding
- Ministry of Education, Science and Culture, Japan [20590181, 21590207]
- Japan Science and Technology Agency (JST)
- Grants-in-Aid for Scientific Research [20590181, 21590207] Funding Source: KAKEN
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Intraepithelial lymphocytes (IELs) are present in the intestinal epithelium. Mechanisms of IELs for the protection of villi from foreign antigens and from infections by micro-organisms have not been sufficiently explained. Although more than 70 % of mouse duodenal and jejunal IELs bear gamma delta TCR (gamma delta IELs), the functions of gamma delta IELs are little investigated. We stimulate gamma delta IELs by anti-CD3 monoclonal antibody (mAb) injection. The mAb activates gamma delta IELs to release Granzyme B (GrB) into the spaces surrounding the gamma delta IELs and intestinal villous epithelial cells (IECs). Released GrB induces DNA fragmentation in IECs independently of Perforin (Pfn). IECs immediately repair their fragmented DNA. Activated IELs reduce their cell size, remain for some time in the epithelium after the activation and are ultimately eliminated without leaving the site. We focus our attention on the response of IELs to the released GrB present in the gap surrounding IELs, after activation, in order to examine whether the released GrB has a similar effect on IELs to that observed on IECs in our previous studies. DNA fragmentation is also induced in IELs together with the repair of fragmented DNA thereafter. The time-kinetics of both events were found to be identical to those observed in IECs. DNA fragmentation in IELs is Pfn-independent. Here, we present Pfn-independent autocrine DNA fragmentation in IELs and the repair of fragmented DNA in IELs and discuss their biological significance. Autocrine DNA fragmentation has never been reported to date in vivo.
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