Piper C, Hainstock E, Yin-Yuan C, et al. Single Cell Immune Profiling Reveals a Developmentally Distinct CD4+ GM-CSF+ T Cell Lineage That Induces GI Tract GVHD. Blood Advances. 2022; (doi: 10.1182/bloodadvances.2021006084).
Through single-cell RNA sequencing analysis, scientists have identified a developmentally distinct subset of T cells in the colon that are implicated in graft-versus-host disease (GVHD). T cells that produce GM-CSF are known to be important pathways for inflammation in the tissues of the gastrointestinal tract. The researchers found that two different CD4+ GM-CSF+ populations are present in the colon during GVHD: one that co-expresses interferon-gamma and one that does not. The subset that was missing IFN-gamma represents an IL-7 responsive, colitogenic T helper GM-CSF lineage. Set apart from other CD4+ populations by its distinct transcriptional profile, unique gene regulatory networks, and non-overlapping TCR repertoire, the cells contributed to pathological impairment in the GI tract. Signaling through the IL-7 receptor, which was not present in the CD4+ GM-CSF+ population that did express IFN-gamma, was necessary to mediate the damage.