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Autocrine DNA fragmentation of intra-epithelial lymphocytes

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...

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Bibliographic Details
Published in:Cell and tissue research 2015-09, Vol.361 (3), p.799
Main Authors: Nanno, Masanobu, Suzuki, Ryuji, Ogata, Masaki, Itoh, Tsunetoshi, Ota, Yuta
Format: Article
Language:English
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Summary: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.
ISSN:0302-766X