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

• Published in: Science (American Association for the Advancement of Science) Vol. 352; no. 6284; pp. 459 - 463
• Main Authors: 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, René A. W., Kallies, Axel, van Gisbergen, Klaas P. J. M.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 22.04.2016; The American Association for the Advancement of Science
• Subjects: Animals; Cellular biology; Gastrointestinal Tract - immunology; Gene Expression Regulation; Genes, Regulator - genetics; Genes, Regulator - physiology; Immune system; Immunologic Memory - genetics; Kidney - immunology; Killer Cells, Natural - immunology; Liver - immunology; Lymphocyte Activation; Lymphocytes; Mice; Mice, Knockout; Natural Killer T-Cells - immunology; Pathogens; Positive Regulatory Domain I-Binding Factor 1; Retention; Skin - immunology; Tissues; Transcription Factors - genetics; Transcription Factors - physiology; Transcription, Genetic; Up-Regulation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.aad2035

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.