Publication Date:
2016-04-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Mackay, Laura K -- Minnich, Martina -- Kragten, Natasja A M -- Liao, Yang -- Nota, Benjamin -- Seillet, Cyril -- Zaid, Ali -- Man, Kevin -- Preston, Simon -- Freestone, David -- Braun, Asolina -- Wynne-Jones, Erica -- Behr, Felix M -- Stark, Regina -- Pellicci, Daniel G -- Godfrey, Dale I -- Belz, Gabrielle T -- Pellegrini, Marc -- Gebhardt, Thomas -- Busslinger, Meinrad -- Shi, Wei -- Carbone, Francis R -- van Lier, Rene A W -- Kallies, Axel -- van Gisbergen, Klaas P J M -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):459-63. doi: 10.1126/science.aad2035.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia. lkmackay@unimelb.edu.au kallies@wehi.edu.au k.vangisbergen@sanquin.nl. ; Research Institute of Molecular Pathology (IMP), Vienna Biocenter (VBC), Vienna, Austria. ; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. ; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. ; Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, AMC, University of Amsterdam, Amsterdam, Netherlands. ; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. ; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. Department of Experimental Immunology, AMC, Amsterdam, Netherlands. ; Department of Microbiology and Immunology, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Australia. Australian Research Council (ARC) Centre of Excellence in Advanced Molecular Imaging, University of Melbourne, Melbourne, Australia. ; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Computing and Information Systems, The University of Melbourne, Melbourne, Australia. ; The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. lkmackay@unimelb.edu.au kallies@wehi.edu.au k.vangisbergen@sanquin.nl. ; Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center (AMC), University of Amsterdam, Amsterdam, Netherlands. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Department of Medical Biology, The University of Melbourne, Melbourne, Australia. Department of Experimental Immunology, AMC, Amsterdam, Netherlands. lkmackay@unimelb.edu.au kallies@wehi.edu.au k.vangisbergen@sanquin.nl.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102484" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Gastrointestinal Tract/immunology
;
*Gene Expression Regulation
;
Genes, Regulator/genetics/*physiology
;
Immunologic Memory/*genetics
;
Kidney/immunology
;
Killer Cells, Natural/*immunology
;
Liver/immunology
;
Lymphocyte Activation
;
Mice
;
Mice, Knockout
;
Natural Killer T-Cells/*immunology
;
Skin/immunology
;
Transcription Factors/genetics/*physiology
;
Transcription, Genetic
;
Up-Regulation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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