MHC Class II Antigen Presentation by the Intestinal Epithelium Initiates Graft-versus-Host Disease and Is Influenced by the Microbiota
This week we profile a recent publication in Immunity from the laboratory of Dr. Geoffrey Hill (pictured) at Fred Hutch.
Can you provide a brief overview of your lab’s current research focus?
Stem cell transplantation is a curative therapy for blood cancers, but outcomes are limited by graft-versus-host disease (GVHD) and infection. In addition, a significant proportion of patients experience relapse of the original blood cancer after transplantation due to a failure of the graft-versus-leukemia (GVL) effect. Our laboratory seeks to understand the immunological mechanisms responsible for GVHD (particularly in the gut where it is often fatal) and GVL. We aim to develop approaches to inhibit the deleterious immune responses responsible for GVHD, whilst improving pathogen and leukemia-specific immunity.
What is the significance of the findings in this publication?
While the effector pathways that mediate GVHD are well established (i.e. donor T cells and cytokines), those that initiate the process remain poorly defined. This study has identified the immunological pathways by which the microbiome interacts with epithelial cells in the gut to allow them to function as antigen presenting cells that initiate GVHD. This information generates logical therapeutic strategies to prevent the initiation of GVHD.
What are the next steps for this research?
We have identified an IL-12-IFNγ axis that is critical to the initiation of GVHD in the gut. We are now planning clinical studies to inhibit IL-12p40/23 before transplantation with the aim of preventing the initiation of gut GVHD.