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

Laura K. Mackay, Martina Minnich, Natasja A.M. Kragten, Yang Liao, Benjamin Nota, Cyril Seillet, Ali Zaid, Kevin Man, Simon Preston, David Freestone, Asolina Braun, Erica Wynne-Jones, Felix M. Behr, Regina Stark, Daniel G. Pellicci, Dale I. Godfrey, Gabrielle T. Belz, Marc Pellegrini, Thomas Gebhardt, Meinrad BusslingerWei Shi, Francis R. Carbone, René A.W. Van Lier, Axel Kallies, Klaas P.J.M. Van Gisbergen

Research output: Contribution to journalArticleResearchpeer-review

298 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)459-463
Number of pages5
JournalScience
Volume352
Issue number6284
DOIs
Publication statusPublished - 22 Apr 2016
Externally publishedYes

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