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

J Clin Invest. 2018 Mar 1;128(3):916-930. doi: 10.1172/JCI89242. Epub 2018 Jan 29.


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.

Keywords: Bone marrow transplantation; Cytokines; Gastroenterology; Immunology; T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic-Leucine Zipper Transcription Factors / metabolism*
  • Biopsy
  • Colon / pathology
  • Female
  • Graft vs Host Disease / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Hematopoietic Stem Cell Transplantation / adverse effects
  • Humans
  • Inflammation
  • Interleukin-7 Receptor alpha Subunit / metabolism*
  • Intestines / immunology
  • Intestines / pathology*
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Prognosis
  • T-Lymphocyte Subsets / metabolism*
  • Transplantation, Homologous


  • BATF protein, human
  • Basic-Leucine Zipper Transcription Factors
  • Batf protein, mouse
  • IL7R protein, human
  • Interleukin-7 Receptor alpha Subunit
  • Granulocyte-Macrophage Colony-Stimulating Factor