Dynamic Imaging of IEL-IEC Co-Cultures Allows for Quantification of CD103-Dependent T Cell Migration

International Journal of Molecular Sciences

Clemens Neufert¹  Karin Enderle¹  Martin Dinkel¹  MarkusF. Neurath¹  Kai Hildner¹  Eva-Maria Spath¹  Sebastian Zundler¹  Benjamin Schmid²  Philipp Tripal² 

[1] Department of Medicine 1, Kussmaul Campus for Medical Research Universitätsklinikum Erlangen, University of Erlangen-Nuremberg, 91052 Erlangen, Germany;Optical Imaging Centre Erlangen (OICE), University of Erlangen-Nuremberg, 91052 Erlangen, Germany;

关键词: intraepithelial lymphocytes;    intestinal organoids;    life cell imaging;    CD103;    lymphocyte migration;   

DOI  :  10.3390/ijms22105148

来源: DOAJ

【 摘 要 】

Intraepithelial lymphocytes (IEL) are widely distributed within the small intestinal epithelial cell (IEC) layer and represent one of the largest T cell pools of the body. While implicated in the pathogenesis of intestinal inflammation, detailed insight especially into the cellular cross-talk between IELs and IECs is largely missing in part due to lacking methodologies to monitor this interaction. To overcome this shortcoming, we employed and validated a murine IEL-IEC (organoids) ex vivo co-culture model system. Using livecell imaging we established a protocol to visualize and quantify the spatio-temporal migratory behavior of IELs within organoids over time. Applying this methodology, we found that IELs lacking CD103 (i.e., integrin alpha E, ITGAE) surface expression usually functioning as a retention receptor for IELs through binding to E-cadherin (CD324) expressing IECs displayed aberrant mobility and migration patterns. Specifically, CD103 deficiency affected the ability of IELs to migrate and reduced their speed during crawling within organoids. In summary, we report a new technology to monitor and quantitatively assess especially migratory characteristics of IELs communicating with IEC ex vivo. This approach is hence readily applicable to study the effects of targeted therapeutic interventions on IEL-IEC cross-talk.

【 授权许可】

Unknown