BATF-dependent IL-7RhiGM-CSF+ T cells control intestinal graft-versus-host disease.
J Clin Invest
; 128(3): 916-930, 2018 03 01.
Article
in En
| MEDLINE
| ID: mdl-29376889
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Granulocyte-Macrophage Colony-Stimulating Factor
/
T-Lymphocyte Subsets
/
Basic-Leucine Zipper Transcription Factors
/
Interleukin-7 Receptor alpha Subunit
/
Graft vs Host Disease
/
Intestines
Type of study:
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
J Clin Invest
Year:
2018
Document type:
Article
Affiliation country:
Germany