The Absence of IL-12Rβ2 Expression on Recipient Nonhematopoietic Cells Diminishes Acute Graft-versus-Host Disease in the Gastrointestinal Tract. J Immunol 2023 Feb 15;210(4):486-495
Date
12/23/2022Pubmed ID
36548465Pubmed Central ID
PMC9938950DOI
10.4049/jimmunol.2200120Scopus ID
2-s2.0-85147317750 (requires institutional sign-in at Scopus site)Abstract
The gastrointestinal (GI) tract is a frequent target organ in acute graft-versus-host disease (aGVHD), which can determine the morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Donor T cells recognize allogeneic Ags presented by host APCs, proliferate, and differentiate into Th1 and Th17 cells that drive GVHD pathogenesis. IL-12 has been shown to play an important role in amplifying the allogeneic response in preclinical and clinical studies. This study demonstrates that IL-12Rβ2 expression on recipient nonhematopoietic cells is required for optimal development of aGVHD in murine models of allo-HCT. aGVHD attenuation by genetic depletion of IL-12R signaling is associated with reduced MHC class II expression by intestinal epithelial cells and maintenance of intestinal integrity. We verified IL-12Rβ2 expression on activated T cells and in the GI tract. This study, to our knowledge, reveals a novel function of IL-12Rβ2 in GVHD pathogenesis and suggests that selectively targeting IL-12Rβ2 on host nonhematopoietic cells may preserve the GI tract after allo-HCT.
Author List
Bastian D, Sui X, Choi HJ, Wu Y, Tian L, Yang K, Liu C, Liu Y, Yu XZAuthors
Yongxia Wu PhD Assistant Professor in the Microbiology and Immunology department at Medical College of WisconsinXue-Zhong Yu MD Professor in the Microbiology and Immunology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Acute DiseaseAnimals
Bone Marrow Transplantation
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Intestines
Mice
Transplantation, Homologous
