%0 Journal Article
%T BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease
%A Andreas Beilhack
%A Andreas Mackensen
%A Benjamin Abendroth
%A Carina Huber
%A Ernst Holler
%A Evelyn Ullrich
%A Georg F. Weber
%A Johanna Rothamer
%A Kai Hildner
%A Maike B邦ttner-Herold
%A Marina Kreutz
%A Markus F. Neurath
%A Sakhila Ghimire
%A Sebastian Zundler
%A Simon Vˋlkl
%A Stefan Rose-John
%A Stefan Wirtz
%A Thomas Longerich
%A Tina Vogler
%A Vera Buchele
%J The Journal of Clinical Investigation
%D 2018
%R 10.1172/JCI89242
%X Acute graft-versus-host disease (GVHD) represents a severe, T cell每driven inflammatory complication following allogeneic hematopoietic cell transplantation (allo-HCT). GVHD often affects the intestine and is associated with a poor prognosis. Although frequently detectable, proinflammatory mechanisms exerted by intestinal tissue每infiltrating Th cell subsets remain to be fully elucidated. Here, we show that the Th17-defining transcription factor basic leucine zipper transcription factor ATF-like (BATF) was strongly regulated across human and mouse intestinal GVHD tissues. Studies in complete MHC-mismatched and minor histocompatibility每mismatched (miHA-mismatched) GVHD models revealed that BATF-expressing T cells were functionally indispensable for intestinal GVHD manifestation. Mechanistically, BATF controlled the formation of colon-infiltrating, IL-7 receptor每positive (IL-7R+), granulocyte-macrophage colony-stimulating factor每positive (GM-CSF+), donor T effector memory (Tem) cells. This T cell subset was sufficient to promote intestinal GVHD, while its occurrence was largely dependent on T cell每intrinsic BATF expression, required IL-7每IL-7R interaction, and was enhanced by GM-CSF. Thus, this study identifies BATF-dependent pathogenic GM-CSF+ effector T cells as critical promoters of intestinal inflammation in GVHD and hence putatively provides mechanistic insight into inflammatory processes previously assumed to be selectively Th17 driven
%U https://www.jci.org/articles/view/89242