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Acute graft-versus-host disease (GVHD) in the gut is common following hematopoetic cell transplantation (HCT) and is associated with high mortality. However, it remains unclear whether Th1 or Th17 CD4+ T cells can initiate acute gut GVHD. In this issue of the JCI, Ullrich and colleagues identified a subset of CD4+ T cells that express high levels of IL-7Rα and granulocyte-macrophage CSF (IL-7RαhiGM-CSF+) cells that are involved in the induction of acute gut GVHD in murine models. The IL-7RαhiGM-CSF+ effector memory cells were BATF dependent, RORγt independent, produced large amounts of GM-CSF and IFN-γ, and released little IL-17. CD4+IL-7RαhiGM-CSF+ cells were not classical Th17 cells but had more of a Th1-like phenotype, despite their dependence on BATF. This work suggests that targeting the IL-7R/BATF/GM-CSF axis has therapeutic potential for treating acute gut GVHD.

Newly found arsons ignite the fire of gut GVHD