BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease

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

Journal

Journal of Clinical Investigation American Society for Clinical Investigation

DOI: 10.1172/JCI89242

Abstract

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.

Authors with CRIS profile

Benjamin Abendroth Juniorprofessur für Pneumologie/ Immunologie Vera Buchele Lehrstuhl für Innere Medizin I Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Georg Weber Department of Surgery Andreas Mackensen Lehrstuhl für Innere Medizin V Markus Neurath Lehrstuhl für Innere Medizin I Kai Hildner Juniorprofessur für Pneumologie/ Immunologie

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE) University of Manchester GB United Kingdom (GB) Goethe-Universität Frankfurt am Main DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Universitätsklinikum Heidelberg DE Germany (DE)

How to cite

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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