T Cell Recruitment to the Intestinal Stem Cell Compartment Drives Immune-Mediated Intestinal Damage after Allogeneic Transplantation

Ya-Yuan Fu, Anastasiya Egorova, Catherine Sobieski, Jason Kuttiyara, Marco Calafiore, Shuichiro Takashima, Hans Clevers, Alan M Hanash

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

The key sites within the gastrointestinal (GI) tract where T cells mediate effector responses and the impact of these responses on intestinal stem cells (ISCs) remain unclear. Using experimental bone marrow transplantation to model immune-mediated GI damage and 3D imaging to analyze T cell localization, we found that the ISC compartment is the primary intestinal site targeted by T cells after transplantation. Recruitment to the crypt base region resulted in direct T cell engagement with the stem cell compartment and loss of crypt base columnar ISCs, which expressed both MHC classes I and II. Vasculature expressing the adhesion molecule MAdCAM-1 clustered near the crypt base, preferentially regulating crypt compartment invasion and ISC reduction without affecting T cell migration to villi. These findings indicate that allogeneic T cells rapidly access the stem cell niche after transplantation, and this targeted recruitment to the stem cell compartment results in ISC loss during immune-mediated GI damage.

Original languageEnglish
Pages (from-to)90-103.e3
JournalImmunity
Volume51
Issue number1
DOIs
Publication statusPublished - 16 Jul 2019

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