T Cell Recruitment to the Intestinal Stem Cell Compartment Drives Immune-Mediated Intestinal Damage after Allogeneic Transplantation
Fu, Ya Yuan; Egorova, Anastasiya; Sobieski, Catherine; Kuttiyara, Jason; Calafiore, Marco; Takashima, Shuichiro; Clevers, Hans; Hanash, Alan M.
(2019) Immunity, volume 51, issue 1, pp. 90 - 103.e3
(Article)
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
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cells during immune-mediated tissue damage occurring after bone marrow transplantation.
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Keywords: allogeneic bone marrow transplantation, beta7 integrin, BMT, graft versus host disease, GVHD, imaging of immunity, intestinal stem cells, ISCs, LPAM, MAdCAM-1, mucosal immunology, Paneth cells, transplantation, Immunology and Allergy, Immunology, Infectious Diseases
ISSN: 1074-7613
Publisher: Cell Press
Note: Funding Information: We thank Jennifer Tsai for her helpful advice, and we thank Jarrod Dudakov for his expert review of our manuscript. We gratefully acknowledge the Memorial Sloan Kettering Cancer Center (MSKCC) Gastroenterology and Nutrition Service and the endoscopy unit staff for their collection of patient biopsies. We also gratefully acknowledge the technical assistance of the MSKCC Molecular Cytology Core Facility and the MSKCC Research Animal Resource Center. This research was supported by NIH award numbers K08-HL115355 (A.M.H.), R01-HL125571 (A.M.H), R01-HL146338 (A.M.H), and P30-CA008748 (MSKCC Core Grant). Support was also received from the Susan and Peter Solomon Divisional Genomics Program , the Parker Institute for Cancer Immunotherapy , the Ludwig Center for Cancer Immunotherapy , and the Anna Fuller Fund (A.M.H.). A.M.H. was also supported by the Amy Strelzer Manasevit Research Program and a Scholar Award from the American Society of Hematology . Y.-Y.F. was supported by a New Investigator Award from the American Society for Blood and Marrow Transplantation (now renamed as the American Society for Transplantation and Cellular Therapy) and Sanofi Genzyme. Funding Information: We thank Jennifer Tsai for her helpful advice, and we thank Jarrod Dudakov for his expert review of our manuscript. We gratefully acknowledge the Memorial Sloan Kettering Cancer Center (MSKCC) Gastroenterology and Nutrition Service and the endoscopy unit staff for their collection of patient biopsies. We also gratefully acknowledge the technical assistance of the MSKCC Molecular Cytology Core Facility and the MSKCC Research Animal Resource Center. This research was supported by NIH award numbers K08-HL115355 (A.M.H.), R01-HL125571 (A.M.H), R01-HL146338 (A.M.H), and P30-CA008748 (MSKCC Core Grant). Support was also received from the Susan and Peter Solomon Divisional Genomics Program, the Parker Institute for Cancer Immunotherapy, the Ludwig Center for Cancer Immunotherapy, and the Anna Fuller Fund (A.M.H.). A.M.H. was also supported by the Amy Strelzer Manasevit Research Program and a Scholar Award from the American Society of Hematology. Y.-Y.F. was supported by a New Investigator Award from the American Society for Blood and Marrow Transplantation (now renamed as the American Society for Transplantation and Cellular Therapy) and Sanofi Genzyme. Y.-Y.F. designed, performed, and analyzed experiments. A.E. C.S. and J.K. performed BMT. M.C. and S.T. helped interpret data. H.C. assisted with Olfm4-GFP experiments. A.M.H. supervised the research. All authors contributed to experimental design, interpretation, and manuscript editing. H.C. is inventor on several patents related to organoids. He is a board member of Roche and a co-founder and stockholder of Surrozen. A.M.H. holds intellectual property related to interleukin-22 and in the past 3 years has performed consulting for Ziopharm and Nexus Global Group. Publisher Copyright: © 2019 Elsevier Inc.
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