Open AccessJournal Article
Hobit and Blimp1 instruct a universal transcriptional program of tissue-residency in lymphocytes
Laura K. Mackay,Martina Minnich,Natasja A. M. Kragten,Cyril Seillet,David Freestone,Gabrielle T. Belz,Meinrad Busslinger,Wei Shi,Francis R. Carbone,R. A. W. Van Lier,Axel Kallies,K van Gisbergen +11 more
TLDR
It is shown that the transcription factor Hobit is specifically up-regulated in Trm cells and, together with related Blimp1, mediates the development of Trms cells in skin, gut, liver, and kidney in mice.Abstract:
Transcription factors define tissue T cells The immune system fights microbial invaders by maintaining multiple lines of defense. For instance, specialized memory T cells [resident memory T cells (Trms)] colonize portals of pathogen entry, such as the skin, lung, and gut, to quickly halt reinfections. Mackay et al. now report that in mice, Trms as well as other tissue-dwelling lymphocyte populations such as natural killer cells share a common transcriptional program driven by the related transcription factors Hobit and Blimp1. Tissue residency and retention of lymphocytes require expression of Hobit and Blimp1, which, among other functions, suppress genes that promote tissue exit. Science, this issue p. 459 Tissue-dwelling lymphocyte populations share a common transcriptional signature. 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.read more
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A molecular cell atlas of the human lung from single-cell RNA sequencing.
Kyle J. Travaglini,Ahmad N. Nabhan,Ahmad N. Nabhan,Lolita Penland,Rahul Sinha,Astrid Gillich,Rene Sit,Stephen Chang,Stephanie D. Conley,Yasuo Mori,Yasuo Mori,Jun Seita,Gerald J. Berry,Joseph B. Shrager,Ross J. Metzger,Christin S. Kuo,Norma Neff,Irving L. Weissman,Stephen R. Quake,Mark A. Krasnow +19 more
TL;DR: Droplet- and plate-based single cell RNA sequencing applied to ~75,000 human cells across all lung tissue compartments and circulating blood, combined with a multi-pronged cell annotation approach, have allowed them to define the gene expression profiles and anatomical locations of 58 cell populations in the human lung.
Journal ArticleDOI
Intratumoral Tcf1+PD-1+CD8+ T Cells with Stem-like Properties Promote Tumor Control in Response to Vaccination and Checkpoint Blockade Immunotherapy.
Imran Siddiqui,Karin Schaeuble,Vijaykumar Chennupati,Silvia A. Fuertes Marraco,Sandra Calderon-Copete,Daniela Pais Ferreira,Santiago J. Carmona,Santiago J. Carmona,Santiago J. Carmona,Leonardo Scarpellino,David Gfeller,David Gfeller,David Gfeller,Sylvain Pradervand,Sanjiv A. Luther,Daniel E. Speiser,Werner Held +16 more
TL;DR: This work identified a subset of tumor‐reactive TILs bearing hallmarks of exhausted cells and central memory cells, including expression of the checkpoint protein PD‐1 and the transcription factor Tcf1 that promote tumor control in response to vaccination and checkpoint blockade immunotherapy.
Journal ArticleDOI
Human Tissue-Resident Memory T Cells Are Defined by Core Transcriptional and Functional Signatures in Lymphoid and Mucosal Sites
Brahma V. Kumar,Wenji Ma,Michelle Miron,Tomer Granot,Rebecca S. Guyer,Dustin J. Carpenter,Takashi Senda,Xiaoyun Sun,Siu-hong Ho,Harvey Lerner,Amy L. Friedman,Yufeng Shen,Donna L. Farber +12 more
TL;DR: A core transcriptional profile within the CD69+ subset of memory CD4+ and CD8+ T cells in lung and spleen that is distinct from that of CD69- TEM cells in tissues and circulation is identified, providing a unifying signature for human TRM and a blueprint for designing tissue-targeted immunotherapies.
Journal ArticleDOI
Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)
Andrea Cossarizza,Hyun-Dong Chang,Andreas Radbruch,Andreas Acs,Dieter Adam,Sabine Adam-Klages,William W. Agace,William W. Agace,Nima Aghaeepour,Mübeccel Akdis,Matthieu Allez,Larissa Nogueira Almeida,Giorgia Alvisi,Graham Anderson,Immanuel Andrä,Francesco Annunziato,Achille Anselmo,Petra Bacher,Cosima T. Baldari,Sudipto Bari,Vincenzo Barnaba,Vincenzo Barnaba,Joana Barros-Martins,Luca Battistini,Wolfgang Bauer,Sabine Baumgart,Nicole Baumgarth,Dirk Baumjohann,Bianka Baying,Mary Bebawy,Burkhard Becher,Wolfgang Beisker,Vladimir Benes,Rudi Beyaert,Alfonso Blanco,Dominic A. Boardman,Christian Bogdan,Jessica G. Borger,Giovanna Borsellino,Philip E. Boulais,Jolene Bradford,Dirk Brenner,Dirk Brenner,Ryan R. Brinkman,Anna E. S. Brooks,Dirk H. Busch,Martin Büscher,Timothy P. Bushnell,Federica Calzetti,Garth Cameron,Ilenia Cammarata,Xuetao Cao,Susanna Cardell,Stefano Casola,Marco A. Cassatella,Andrea Cavani,Antonio Celada,Lucienne Chatenoud,Pratip K. Chattopadhyay,Sue Chow,Eleni Christakou,Eleni Christakou,Luka Cicin-Sain,Mario Clerici,Federico Colombo,Laura Cook,Anne Cooke,Andrea M. Cooper,Alexandra J. Corbett,Antonio Cosma,Lorenzo Cosmi,Pierre Coulie,Ana Cumano,Ljiljana Cvetkovic,Van Duc Dang,Chantip Dang-Heine,Martin S. Davey,Derek Davies,Sara De Biasi,Genny Del Zotto,Gelo Victoriano Dela Cruz,Michael Delacher,Silvia Della Bella,Paolo Dellabona,Günnur Deniz,Mark C. Dessing,James P. Di Santo,Andreas Diefenbach,Francesco Dieli,Andreas Dolf,Thomas Dörner,Regine J. Dress,Diana Dudziak,Michael L. Dustin,Charles-Antoine Dutertre,Charles-Antoine Dutertre,Friederike Ebner,Sidonia B G Eckle,Matthias Edinger,Pascale Eede,Götz R. A. Ehrhardt,Marcus Eich,Pablo Engel,Britta Engelhardt,Anna Erdei,Charlotte Esser,Bart Everts,Maximilien Evrard,Christine S. Falk,Todd A. Fehniger,Mar Felipo-Benavent,Helen Ferry,Markus Feuerer,Andrew Filby,Kata Filkor,Simon Fillatreau,Marie Follo,Irmgard Förster,John Bellamy Foster,Gemma A. Foulds,Britta Frehse,Paul S. Frenette,Stefan Frischbutter,Wolfgang Fritzsche,David W. Galbraith,David W. Galbraith,Anastasia Gangaev,Natalio Garbi,Brice Gaudilliere,Ricardo T. Gazzinelli,Ricardo T. Gazzinelli,Jens Geginat,Wilhelm Gerner,Nicholas A Gherardin,Kamran Ghoreschi,Lara Gibellini,Florent Ginhoux,Florent Ginhoux,Florent Ginhoux,Keisuke Goda,Keisuke Goda,Keisuke Goda,Dale I. Godfrey,Christoph Goettlinger,José M. González-Navajas,Carl S. Goodyear,Andrea Gori,Jane L. Grogan,Daryl Grummitt,Andreas Grützkau,Claudia Haftmann,Jonas Hahn,Hamida Hammad,Günter J. Hämmerling,Leo Hansmann,Göran K. Hansson,Christopher M. Harpur,Susanne Hartmann,Andrea Hauser,Anja E. Hauser,David L. Haviland,David W. Hedley,Daniela C. Hernández,Guadalupe Herrera,Martin Herrmann,Christoph Hess,Christoph Hess,Thomas Höfer,Petra Hoffmann,Kristin A. Hogquist,Tristan Holland,Thomas Höllt,Thomas Höllt,Rikard Holmdahl,Pleun Hombrink,Jessica P. Houston,Bimba F. Hoyer,Bo Huang,Fang-Ping Huang,Johanna Huber,Jochen Huehn,Michael Hundemer,Christopher A. Hunter,William Hwang,William Hwang,Anna Iannone,Florian Ingelfinger,Sabine Ivison,Hans-Martin Jäck,Peter K. Jani,Beatriz Jávega,Stipan Jonjić,Toralf Kaiser,Tomas Kalina,Thomas Kamradt,Stefan H. E. Kaufmann,Baerbel Keller,Steven L. C. Ketelaars,Ahad Khalilnezhad,Ahad Khalilnezhad,Srijit Khan,Jan Kisielow,Paul Klenerman,Jasmin Knopf,Hui-Fern Koay,Katja Kobow,Jay K. Kolls,Wan Ting Kong,Manfred Kopf,Thomas Korn,Katharina Kriegsmann,Hendy Kristyanto,Thomas Kroneis,Andreas Krueger,J. Kühne,Christian Kukat,Désirée Kunkel,Heike Kunze-Schumacher,Tomohiro Kurosaki,Christian Kurts,Pia Kvistborg,Immanuel Kwok,Immanuel Kwok,Jonathan J M Landry,Olivier Lantz,Paola Lanuti,Francesca LaRosa,Agnès Lehuen,Salomé LeibundGut-Landmann,Michael D. Leipold,Leslie Y. T. Leung,Megan K. Levings,Andreia C. Lino,Francesco Liotta,Virginia Litwin,Yanling Liu,Hans-Gustaf Ljunggren,Michael Lohoff,Giovanna Lombardi,Lilly Lopez,Miguel López-Botet,Amy E. Lovett-Racke,Erik Lubberts,Hervé Luche,Burkhard Ludewig,Enrico Lugli,Sebastian Lunemann,Holden T. Maecker,Laura Maggi,Orla Maguire,Florian Mair,Kerstin H. Mair,Alberto Mantovani,Rudolf A. Manz,Aaron J. Marshall,Alicia Martínez-Romero,Gloria Martrus,Ivana Marventano,Wlodzimierz Maslinski,Giuseppe Matarese,Anna Vittoria Mattioli,Christian Maueröder,Christian Maueröder,Alessio Mazzoni,James McCluskey,Mairi McGrath,Helen M. McGuire,Iain B. McInnes,Henrik E. Mei,Fritz Melchers,Susanne Melzer,Dirk Mielenz,Stephen D. Miller,Kingston H. G. Mills,Hans Minderman,Jenny Mjösberg,Jenny Mjösberg,Jonni S. Moore,Barry Moran,Lorenzo Moretta,Tim R. Mosmann,Susann Müller,Gabriele Multhoff,Luis E. Muñoz,Christian Münz,Toshinori Nakayama,Milena Nasi,Katrin Neumann,Lai Guan Ng,Antonia Niedobitek,Sussan Nourshargh,Gabriel Núñez,José-Enrique O'Connor,A Ochel,Anna E. 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Wing,Rieke Winkelmann,Thomas Winkler,Oliver F. Wirz,Alicia Wong,Peter Wurst,Jennie H M Yang,Jennie H M Yang,Juhao Yang,Maria Yazdanbakhsh,Liping Yu,Alice Yue,Hanlin Zhang,Yi Zhao,Susanne Ziegler,Christina E. Zielinski,Jakob Zimmermann,Arturo Zychlinsky +462 more
TL;DR: These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community providing the theory and key practical aspects offlow cytometry enabling immunologists to avoid the common errors that often undermine immunological data.
Journal ArticleDOI
Human T Cell Development, Localization, and Function throughout Life.
TL;DR: How human T cells develop and provide essential immune protection at different life stages is discussed and tissue localization and subset delineation are highlighted as key determinants of the T cell functional role in immune responses.
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