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PMID:27102484

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Citation

Mackay, LK, Minnich, M, Kragten, NA, Liao, Y, Nota, B, Seillet, C, Zaid, A, Man, K, Preston, S, Freestone, D, Braun, A, Wynne-Jones, E, Behr, FM, Stark, R, Pellicci, DG, Godfrey, DI, Belz, GT, Pellegrini, M, Gebhardt, T, Busslinger, M, Shi, W, Carbone, FR, van Lier, RA, Kallies, A and van Gisbergen, KP (2016) Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science 352:459-63

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.

Links

PubMed Online version:10.1126/science.aad2035

Keywords

Animals; Gastrointestinal Tract/immunology; Gene Expression Regulation; Genes, Regulator/genetics; Genes, Regulator/physiology; Immunologic Memory/genetics; Kidney/immunology; Killer Cells, Natural/immunology; Liver/immunology; Lymphocyte Activation; Mice; Mice, Knockout; Natural Killer T-Cells/immunology; Positive Regulatory Domain I-Binding Factor 1; Skin/immunology; Transcription Factors/genetics; Transcription Factors/physiology; Transcription, Genetic; Up-Regulation

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