Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes

LK Mackay, M Minnich, NAM Kragten, Y Liao, B Nota… - Science, 2016 - science.org
LK Mackay, M Minnich, NAM Kragten, Y Liao, B Nota, C Seillet, A Zaid, K Man, S Preston
Science, 2016science.org
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry,
where they provide immediate protection against reinfection. To enforce tissue retention,
Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress;
however, a Trm-specific transcriptional regulator has not been identified. Here, we show that
the transcription factor Hobit is specifically up-regulated in Trm cells and, together with
related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice …
Tissue-resident memory T (Trm) cells permanently localize to portals of pathogen entry, where they provide immediate protection against reinfection. To enforce tissue retention, Trm cells up-regulate CD69 and down-regulate molecules associated with tissue egress; however, a Trm-specific transcriptional regulator has not been identified. Here, we show that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trm cells in skin, gut, liver, and kidney in mice. The Hobit-Blimp1 transcriptional module is also required for other populations of tissue-resident lymphocytes, including natural killer T (NKT) cells and liver-resident NK cells, all of which share a common transcriptional program. Our results identify Hobit and Blimp1 as central regulators of this universal program that instructs tissue retention in diverse tissue-resident lymphocyte populations.
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