Ullrich E, Abendroth B, Rothamer J, Huber C, Büttner-Herold M, Buchele V, Vogler T, Longerich T, Zundler S, Völkl S, Beilhack A, Rose-John S, Wirtz S, Weber G, Ghimire S, Kreutz M, Holler E, Mackensen A, Neurath M, Hildner K (2018)
Publication Type: Journal article
Publication year: 2018
DOI: 10.1172/JCI89242
Acute graft-versus-host disease (GVHD) represents a severe, T cell-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-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-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-positive (IL-7R+), granulocyte-macrophage colony-stimulating factor-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-intrinsic BATF expression, required IL-7-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.
APA:
Ullrich, E., Abendroth, B., Rothamer, J., Huber, C., Büttner-Herold, M., Buchele, V.,... Hildner, K. (2018). BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease. Journal of Clinical Investigation. https://doi.org/10.1172/JCI89242
MLA:
Ullrich, Evelyn, et al. "BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease." Journal of Clinical Investigation (2018).
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