Dataset Information

Human Wnt/β-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation.

ABSTRACT: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adoptive immunotherapy for the treatment of hematological malignancies. Detrimental graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is required to accomplish the uncoupling of GVHD from GVL. Here, we evaluated the role of β-catenin in this process. Using a unique mouse model of transgenic overexpression of human β-catenin (Cat-Tg) in an allo-HSCT model, we show here that T cells from Cat-Tg mice did not cause GVHD, and surprisingly, Cat-Tg T cells maintained the GVL effect. Donor T cells from Cat-Tg mice exhibited significantly lower inflammatory cytokine production and reduced donor T cell proliferation, while upregulating cytotoxic mediators that resulted in enhanced cytotoxicity. RNA sequencing revealed changes in the expression of 1169 genes for CD4, and 1006 genes for CD8+ T cells involved in essential aspects of immune response and GVHD pathophysiology. Altogether, our data suggest that β-catenin is a druggable target for developing therapeutic strategies to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.

SUBMITTER: Mammadli M

PROVIDER: S-EPMC8345079 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Human Wnt/β-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation.

Mammadli Mahinbanu M Harris Rebecca R Mahmudlu Sara S Verma Anjali A May Adriana A Dhawan Rohan R Waickman Adam T AT Sen Jyoti Misra JM August Avery A Karimi Mobin M

Cancers 20210728 15

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most widely applied forms of adoptive immunotherapy for the treatment of hematological malignancies. Detrimental graft-versus-host disease (GVHD), but also beneficial graft-versus-leukemia (GVL) effects occurring after allo-HSCT are largely mediated by alloantigen-reactive donor T cells in the graft. Separating GVHD from GVL effects is a formidable challenge, and a greater understanding of donor T cell biology is requir ...[more]

PMID: 34359702

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Dataset Information

Human Wnt/β-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation.

Publications

Human Wnt/β-Catenin Regulates Alloimmune Signaling during Allogeneic Transplantation.

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