Host-Derived Serine Protease Inhibitor 6 Provides Granzyme B-Independent Protection of Intestinal Epithelial Cells in Murine Graft-versus-Host Disease.

ABSTRACT: Graft-versus-host disease (GVHD) is a serious complication after allogeneic hematopoietic cell transplantation (allo-HCT) that limits the therapeutic potential of this treatment. Host antigen-presenting cells (APCs) play a vital role in activating donor T cells that subsequently use granzyme B (GzmB) and other cytotoxic molecules to damage host normal tissues. Serine protease inhibitor 6 (Spi6), known as the sole endogenous inhibitor of GzmB, has been implicated in protecting T cells and APCs against GzmB-inflicted damage. In this study we used murine models to examine the previously unknown role of host-derived Spi6 in GVHD pathogenesis. Our results indicated that host Spi6 deficiency exacerbated GVHD as evidenced by significantly increased lethality and clinical and histopathologic score

SUBMITTER: Mohammadpour H 

PROVIDER: S-EPMC6286216 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature