| Literature DB >> 25846718 |
Yongxia Wu1, David Bastian2, Steven Schutt2, Hung Nguyen2, Jianing Fu2, Jessica Heinrichs2, Changqing Xia3, Xue-Zhong Yu4.
Abstract
Graft-versus-host disease (GVHD), in both its acute (aGVHD) and chronic (cGVHD) forms, remains a major obstacle impeding successful allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells, in particular pathogenic T helper (Th) 1 and Th17 subsets, are a driving force for the induction of GVHD. IL-12 and IL-23 cytokines share a common p40 subunit and play a critical role in driving Th1 differentiation and in stabilizing the Th17 phenotype, respectively. In our current study, we hypothesized that p40 is an essential cytokine in the development of GVHD. By using p40-deficient mice, we found that both donor- and host-derived p40 contribute to the development of aGVHD. Neutralization of p40 with an anti-p40 mAb inhibited Th1- and Th17-polarization in vitro. Furthermore, anti-p40 treatment reduced aGVHD severity while preserving the graft-versus-leukemia (GVL) activity. Alleviation of aGVHD was associated with an increase of Th2 differentiation and a decrease of Th1 and Th17 effector T cells in the GVHD target organs. In addition, anti-p40 treatment attenuated the severity of sclerodermatous cGVHD. These results provide a strong rationale that blockade of p40 may represent a promising therapeutic strategy in preventing and treating aGVHD and cGVHD while sparing the GVL effect after allo-HSCT.Entities:
Keywords: Antigen-presenting cells; Graft-versus-host disease; IL-12; IL-23; T cell differentiation; T cell migration; T cells; p40
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Year: 2015 PMID： 25846718 PMCID： PMC4466028 DOI： 10.1016/j.bbmt.2015.03.016
Source DB: PubMed Journal: Biol Blood Marrow Transplant ISSN： 1083-8791 Impact factor: 5.742