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 Busslinger & 5 others Wei Shi, Francis R. Carbone, René A.W. Van Lier, Axel Kallies, Klaas P.J.M. Van Gisbergen

Research output: Contribution to journalArticleResearchpeer-review

205 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

Cite this

Mackay, L. K., Minnich, M., Kragten, N. A. M., Liao, Y., Nota, B., Seillet, C., ... Van Gisbergen, K. P. J. M. (2016). Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science, 352(6284), 459-463. https://doi.org/10.1126/science.aad2035
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. / Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. In: Science. 2016 ; Vol. 352, No. 6284. pp. 459-463.
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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.",
author = "Mackay, {Laura K.} and Martina Minnich and Kragten, {Natasja A.M.} and Yang Liao and Benjamin Nota and Cyril Seillet and Ali Zaid and Kevin Man and Simon Preston and David Freestone and Asolina Braun and Erica Wynne-Jones and Behr, {Felix M.} and Regina Stark and Pellicci, {Daniel G.} and Godfrey, {Dale I.} and Belz, {Gabrielle T.} and Marc Pellegrini and Thomas Gebhardt and Meinrad Busslinger and Wei Shi and Carbone, {Francis R.} and {Van Lier}, {Ren{\'e} A.W.} and Axel Kallies and {Van Gisbergen}, {Klaas P.J.M.}",
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Mackay, LK, Minnich, M, Kragten, NAM, 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, RAW, Kallies, A & Van Gisbergen, KPJM 2016, 'Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes', Science, vol. 352, no. 6284, pp. 459-463. https://doi.org/10.1126/science.aad2035

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

In: Science, Vol. 352, No. 6284, 22.04.2016, p. 459-463.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Mackay, Laura K.

AU - Minnich, Martina

AU - Kragten, Natasja A.M.

AU - Liao, Yang

AU - Nota, Benjamin

AU - Seillet, Cyril

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AU - Man, Kevin

AU - Preston, Simon

AU - Freestone, David

AU - Braun, Asolina

AU - Wynne-Jones, Erica

AU - Behr, Felix M.

AU - Stark, Regina

AU - Pellicci, Daniel G.

AU - Godfrey, Dale I.

AU - Belz, Gabrielle T.

AU - Pellegrini, Marc

AU - Gebhardt, Thomas

AU - Busslinger, Meinrad

AU - Shi, Wei

AU - Carbone, Francis R.

AU - Van Lier, René A.W.

AU - Kallies, Axel

AU - Van Gisbergen, Klaas P.J.M.

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AB - 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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Mackay LK, Minnich M, Kragten NAM, Liao Y, Nota B, Seillet C et al. Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes. Science. 2016 Apr 22;352(6284):459-463. https://doi.org/10.1126/science.aad2035