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Reis BS, Hoytema van Konijnenburg DP, Grivennikov SI, Mucida D
Transcription Factor T-bet Regulates Intraepithelial Lymphocyte Functional Maturation
Immunity (2014) 41:244-56.
The intestinal epithelium harbors large populations of activated and memory lymphocytes, yet these cells do not cause tissue damage in the steady state. We investigated how intestinal T cell effector differentiation is regulated upon migration to the intestinal epithelium. Using gene loss- and gain-of-function strategies, as well as reporter approaches, we showed that cooperation between the transcription factors T-bet and Runx3 resulted in suppression of conventional CD4(+) T helper functions and induction of an intraepithelial lymphocyte (IEL) program that included expression of IEL markers such as CD8alphaalpha homodimers. Interferon-gamma sensing and T-bet expression by CD4(+) T cells were both required for this program, which was distinct from conventional T helper differentiation but shared by other IEL populations, including TCRalphabeta(+)CD8alphaalpha(+) IELs. We conclude that the gut environment provides cues for IEL maturation through the interplay between T-bet and Runx3, allowing tissue-specific adaptation of mature T lymphocytes.
Publication Date: 2014-08-21.
PMCID: 4287410
Last updated on Wednesday, March 04, 2020