T cell recruitment to the intestinal stem cell compartment drives immune-mediated intestinal damage after allogeneic transplantation Journal Article

   

Authors:	Fu, Y. Y.; Egorova, A.; Sobieski, C.; Kuttiyara, J.; Calafiore, M.; Takashima, S.; Clevers, H.; Hanash, A. M.
Article Title:	T cell recruitment to the intestinal stem cell compartment drives immune-mediated intestinal damage after allogeneic transplantation
Abstract:	The key sites within the gastrointestinal tract where T cells mediate effector responses and their impact on intestinal stem cells remain unclear. Using 3D microscopy, Fu et al. visualize T cell spatial localization within the gastrointestinal tract, revealing the stem cell compartment as the primary intestinal target of allogeneic T cells during immune-mediated tissue damage occurring after bone marrow transplantation. © 2019 Elsevier Inc. 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. © 2019 Elsevier Inc.
Keywords:	transplantation; gvhd; beta7 integrin; paneth cells; bmt; iscs; madcam-1; allogeneic bone marrow transplantation; graft versus host disease; mucosal immunology; imaging of immunity; intestinal stem cells; lpam
Journal Title:	Immunity
Volume:	51
Issue:	1
ISSN:	1074-7613
Publisher:	Cell Press
Date Published:	2019-07-16
Start Page:	90
End Page:	103.e3
Language:	English
DOI:	10.1016/j.immuni.2019.06.003
PROVIDER:	scopus
PUBMED:	31278057
PMCID:	PMC7239328
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85068662217&doi=10.1016%2fj.immuni.2019.06.003&partnerID=40&md5=f76a4cdcf2d226d7b51efe09f1c306aa
Notes:	Article -- Export Date: 2 August 2019 -- Source: Scopus

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