Galectin-3 expression in donor T cells reduces GvHD severity and lethality after allogeneic hematopoietic cell transplantation.

Autor:	Mohammadpour H; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. Electronic address: hemn.mohammadpour@roswellpark.org., Tsuji T; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., MacDonald CR; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Sarow JL; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Rosenheck H; Department of Medicine, Transplant and Cellular Therapy Program, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Daneshmandi S; Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Choi JE; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Qiu J; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Matsuzaki J; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Witkiewicz AK; Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Attwood K; Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Blazar BR; Department of Pediatrics, Division of Blood & Marrow Transplant & Cellular Therapy, University of Minnesota, Minneapolis, MN 55455, USA., Odunsi K; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., Repasky EA; Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA., McCarthy PL; Center for Immunotherapy, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA. Electronic address: philip.mccarthy@roswellpark.org.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Mar 28; Vol. 42 (3), pp. 112250. Date of Electronic Publication: 2023 Mar 15.
DOI:	10.1016/j.celrep.2023.112250
Abstrakt:	Abundant donor cytotoxic T cells that attack normal host organs remain a major problem for patients receiving allogeneic hematopoietic cell transplantation (allo-HCT). Despite an increase in our knowledge of the pathobiology of acute graft versus host disease (aGvHD), the mechanisms regulating the proliferation and function of donor T cells remain unclear. Here, we show that activated donor T cells express galectin-3 (Gal-3) after allo-HCT. In both major and minor histocompatibility-mismatched models of murine aGvHD, expression of Gal-3 is associated with decreased T cell activation and suppression of the secretion of effector cytokines, including IFN-γ and GM-CSF. Mechanistically, Gal-3 results in activation of NFAT signaling, which can induce T cell exhaustion. Gal-3 overexpression in human T cells prevents severe disease by suppressing cytotoxic T cells in xenogeneic aGvHD models. Together, these data identify the Gal-3-dependent regulatory pathway in donor T cells as a critical component of inflammation in aGvHD. Competing Interests: Declaration of interests P.L.M. has received honoraria from and participated in advisory boards for Bristol Myers Squibb, Bluebird, Celgene, Janssen, Juno, Karyopharm, Magenta Therapeutics, Oncopeptides and Takeda. B.R.B serves on advisory boards for Magenta Therapeutics and BlueRock Therapeutics; receives research funding from BlueRock Therapeutics, Rheos Medicines, Equilibre Pharmaceuticals Corp., and Carisma Therapeutics, Inc.; and is a co-founder of Tmunity Therapeutics. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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