Mutual expression of Runx3 and ThPOK regulates intestinal CD4(+) T cell immunity

The gut mucosa hosts large numbers of activated lymphocytes, exposed to stimuli from diet, microbiota and pathogens. Although CD4(+) T cells are crucial for defense, intestinal homeostasis precludes exaggerated response towards luminal contents, harmful or not. We investigated mechanisms used by CD4(+) T cells to avoid excessive activation within the intestine. Using genetic tools to label and interfere with T cell development transcription factors we show that CD4(+) T cells acquired CD8-lineage transcription factor Runx3 while losing CD4-lineage transcription factor ThPOK along with their T(H)17 differentiation and colitogenic potential, in a transforming growth factor-β (TGF-β) and retinoic-acid-dependent manner. These results show a remarkable plasticity in the CD4(+) T cell lineage that allows chronic exposure to luminal antigens without pathological inflammation.