Ullrich, Evelyn and Abendroth, Benjamin and Rothamer, Johanna and Huber, Carina and Buettner-Herold, Maike and Buchele, Vera and Vogler, Tina and Longerich, Thomas and Zundler, Sebastian and Voelkl, Simon and Beilhack, Andreas and Rose-John, Stefan and Wirtz, Stefan and Weber, Georg F. and Ghimire, Sakhila and Kreutz, Marina and Holler, Ernst and Mackensen, Andreas and Neurath, Markus F. and Hildner, Kai (2018) BATF-dependent IL-7R(hi)GM-CSF+ T cells control intestinal graft-versus-host disease. JOURNAL OF CLINICAL INVESTIGATION, 128 (3). pp. 916-930. ISSN 0021-9738, 1558-8238
Full text not available from this repository. (Request a copy)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 coloninfiltrating, 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ROR-GAMMA-T; BONE-MARROW-TRANSPLANTATION; GM-CSF; EPITHELIAL-CELLS; PLASMA-LEVELS; HELPER-CELLS; T(H)17 CELLS; ACUTE GVHD; INTERLEUKIN-7; IL-7; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2020 12:14 |
| Last Modified: | 12 Mar 2020 12:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14928 |
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