Articles

  • Article |

    HIV infection results in T cell dysfunction. Kaufmann and colleagues demonstrate that HIV infection results in an alterated differentation of HIV-specific CD4+ T cells that is only partially reversed by antiretroviral therapy and generation of dysfunctional T cells with a follicular helper-like phenotype.

    • Antigoni Morou
    • , Elsa Brunet-Ratnasingham
    • , Mathieu Dubé
    • , Roxanne Charlebois
    • , Eloi Mercier
    • , Sam Darko
    • , Nathalie Brassard
    • , Krystelle Nganou-Makamdop
    • , Sahaana Arumugam
    • , Gabrielle Gendron-Lepage
    • , Lifei Yang
    • , Julia Niessl
    • , Amy E. Baxter
    • , James M. Billingsley
    • , Premeela A. Rajakumar
    • , François Lefebvre
    • , R. Paul Johnson
    • , Cécile Tremblay
    • , Jean-Pierre Routy
    • , Richard T. Wyatt
    • , Andrés Finzi
    • , Daniel C. Douek
    •  & Daniel E. Kaufmann
  • Article |

    Treg cells obstruct effective anticancer responses. Lee and colleagues describe a Treg cell biomarker signature that is strongly associated with enhanced suppression and progression of human breast cancer.

    • Lei Wang
    • , Diana L. Simons
    • , Xuyang Lu
    • , Travis Y. Tu
    • , Shawn Solomon
    • , Roger Wang
    • , Anthony Rosario
    • , Christian Avalos
    • , Daniel Schmolze
    • , John Yim
    • , James Waisman
    •  & Peter P. Lee
  • Article |

    Systemic lupus erythematosus (SLE) is characterized by autoantibodies produced by pathogenic B cells. Boss, Sanz and colleagues show that SLE-associated epigenetic changes exist in gene regulatory programs in resting naive B cells, before their differentiation into antibody-producing plasma cells.

    • Christopher D. Scharer
    • , Emily L. Blalock
    • , Tian Mi
    • , Benjamin G. Barwick
    • , Scott A. Jenks
    • , Tsuneo Deguchi
    • , Kevin S. Cashman
    • , Bridget E. Neary
    • , Dillon G. Patterson
    • , Sakeenah L. Hicks
    • , Arezou Khosroshahi
    • , F. Eun-Hyung Lee
    • , Chungwen Wei
    • , Iñaki Sanz
    •  & Jeremy M. Boss
  • Article |

    Innate lymphoid cells (ILCs) can exhibit considerable plasticity. Humbles and colleagues identify a subpopulation of ILC2s in humans that can convert to proinflammatory ILC3s with implications for human skin diseases.

    • Jochem H. Bernink
    • , Yoichiro Ohne
    • , Marcel B. M. Teunissen
    • , Jingya Wang
    • , Jincheng Wu
    • , Lisette Krabbendam
    • , Christine Guntermann
    • , Richard Volckmann
    • , Jan Koster
    • , Sophie van Tol
    • , Ivan Ramirez
    • , Yashaswi Shrestha
    • , Menno A. de Rie
    • , Hergen Spits
    • , Xavier Romero Ros
    •  & Alison A. Humbles
  • Article |

    O’Sullivan and colleagues show that liver-resident type 1 ILCs have enhanced protective effector responses to secondary challenge with mouse cytomegalovirus, dependent on the viral glycoprotein m12.

    • Orr-El Weizman
    • , Eric Song
    • , Nicholas M. Adams
    • , Andrew D. Hildreth
    • , Luke Riggan
    • , Chirag Krishna
    • , Oscar A. Aguilar
    • , Christina S. Leslie
    • , James R. Carlyle
    • , Joseph C. Sun
    •  & Timothy E. O’Sullivan
  • Article |

    Cerebral ischemia activates innate immune responses in injured brain lesions. Andreasson and colleagues show TREM1 is upregulated after stroke and amplifies these proinflammatory responses by peripheral CD11b+ myeloid cells in both the ischemic brain and distally in the intestine.

    • Qingkun Liu
    • , Emily M. Johnson
    • , Rachel K. Lam
    • , Qian Wang
    • , Hong Bo Ye
    • , Edward N. Wilson
    • , Paras S. Minhas
    • , Ling Liu
    • , Michelle S. Swarovski
    • , Stephanie Tran
    • , Jing Wang
    • , Swapnil S. Mehta
    • , Xi Yang
    • , Joshua D. Rabinowitz
    • , Samuel S. Yang
    • , Mehrdad Shamloo
    • , Christoph Mueller
    • , Michelle L. James
    •  & Katrin I. Andreasson
  • Article |

    The membrane tetraspan protein MS4A4A is expressed on tissue-resident and tumor-associated macrophages. Locati and colleagues show that MS4A4A colocalizes with the β-glucan receptor dectin-1 to enhance cytokine and reactive oxygen species production and to enhance NK cell–mediated control of tumor metastasis.

    • Irene Mattiola
    • , Federica Tomay
    • , Maria De Pizzol
    • , Rita Silva-Gomes
    • , Benedetta Savino
    • , Tamara Gulic
    • , Andrea Doni
    • , Silvia Lonardi
    • , Marie Astrid Boutet
    • , Alessandra Nerviani
    • , Roberta Carriero
    • , Martina Molgora
    • , Matteo Stravalaci
    • , Diego Morone
    • , Irina N. Shalova
    • , Yunquin Lee
    • , Subhra K. Biswas
    • , Giovanna Mantovani
    • , Marina Sironi
    • , Costantino Pitzalis
    • , William Vermi
    • , Barbara Bottazzi
    • , Alberto Mantovani
    •  & Massimo Locati
  • Article |

    IFN-λ has important innate immune system functions at mucosal surfaces, but its importance in adaptive immunity is largely unknown. Using an influenza infection model, Gale and colleagues demonstrate that IFN-λ is essential for effective adaptive cellular immunity in the lung.

    • Emily A. Hemann
    • , Richard Green
    • , J. Bryan Turnbull
    • , Ryan A. Langlois
    • , Ram Savan
    •  & Michael Gale Jr
  • Article |

    Ginhoux and colleagues show that the priming of mouse hematopoietic progenitor cells toward the pDC lineage occurs at the common lymphoid progenitor stage.

    • Regine J. Dress
    • , Charles-Antoine Dutertre
    • , Amir Giladi
    • , Andreas Schlitzer
    • , Ivy Low
    • , Nurhidaya Binte Shadan
    • , Alicia Tay
    • , Josephine Lum
    • , Muhammad Faris Bin Mohd Kairi
    • , You Yi Hwang
    • , Etienne Becht
    • , Yang Cheng
    • , Marion Chevrier
    • , Anis Larbi
    • , Evan W. Newell
    • , Ido Amit
    • , Jinmiao Chen
    •  & Florent Ginhoux
  • Article |

    Colonna and colleagues show that human innate lymphoid cells undergo conversion from ILC3s into ILC1-like cells in tissues in vivo.

    • Marina Cella
    • , Ramya Gamini
    • , Cristiane Sécca
    • , Patrick L. Collins
    • , Shanrong Zhao
    • , Vincent Peng
    • , Michelle L. Robinette
    • , Jorge Schettini
    • , Konstantin Zaitsev
    • , William Gordon
    • , Jennifer K. Bando
    • , Kentaro Yomogida
    • , Victor Cortez
    • , Catrina Fronick
    • , Robert Fulton
    • , Lih-Ling Lin
    • , Susan Gilfillan
    • , Richard A. Flavell
    • , Liang Shan
    • , Maxim N. Artyomov
    • , Michael Bowman
    • , Eugene M. Oltz
    • , Scott A. Jelinsky
    •  & Marco Colonna
  • Article |

    Treg cells are essential for self-tolerance. Huseby and colleagues identify multiple de facto Treg cell self-peptides and show that Treg cells are exported from the thymus within a defined postnatal developmental window that is controlled by their increased negative selection.

    • Brian D. Stadinski
    • , Sydney J. Blevins
    • , Nicholas A. Spidale
    • , Brian R. Duke
    • , Priya G. Huseby
    • , Lawrence J. Stern
    •  & Eric S. Huseby
  • Article |

    Long-lived, self-renewing ‘progenitor-like’ CD8+ T cells can arise during chronic viral infection or in cancer. Wu and colleagues identify the transcription factor TOX as essential to endow ‘stemness’ and long-term persistence in the face of chronic infection.

    • Chen Yao
    • , Hong-Wei Sun
    • , Neal E. Lacey
    • , Yun Ji
    • , E. Ashley Moseman
    • , Han-Yu Shih
    • , Elisabeth F. Heuston
    • , Martha Kirby
    • , Stacie Anderson
    • , Jun Cheng
    • , Omar Khan
    • , Robin Handon
    • , Julie Reilley
    • , Jessica Fioravanti
    • , Jinhui Hu
    • , Selamawit Gossa
    • , E. John Wherry
    • , Luca Gattinoni
    • , Dorian B. McGavern
    • , John J. O’Shea
    • , Pamela L. Schwartzberg
    •  & Tuoqi Wu
  • Article |

    Multiple genetic variants have been identified that influence the outcome of HIV infection. Carrington and colleagues investigate the mechanism of one of the strongest variants, rs1015164, and show that it influences expression of a lncRNA controlling CCR5 expression.

    • Smita Kulkarni
    • , Alexandra Lied
    • , Viraj Kulkarni
    • , Marijana Rucevic
    • , Maureen P. Martin
    • , Victoria Walker-Sperling
    • , Stephen K. Anderson
    • , Rodger Ewy
    • , Sukhvinder Singh
    • , Hoang Nguyen
    • , Paul J. McLaren
    • , Mathias Viard
    • , Vivek Naranbhai
    • , Chengcheng Zou
    • , Zhansong Lin
    • , Hiroyuki Gatanaga
    • , Shinichi Oka
    • , Masafumi Takiguchi
    • , Chloe L. Thio
    • , Joseph Margolick
    • , Gregory D. Kirk
    • , James J. Goedert
    • , W. Keith Hoots
    • , Steven G. Deeks
    • , David W. Haas
    • , Nelson Michael
    • , Bruce Walker
    • , Sylvie Le Gall
    • , Fatema Z. Chowdhury
    • , Xu G. Yu
    •  & Mary Carrington
  • Article |

    IL-15 has important functions in the activation and homeostasis of cytotoxic T lymphocytes (CTLs) and NK cells. Sun and colleagues demonstrate that the deubiquitinase Otub1 controls CTLs and NK cells in a cell-intrinsic manner by negatively regulating IL-15 signaling.

    • Xiaofei Zhou
    • , Jiayi Yu
    • , Xuhong Cheng
    • , Baoyu Zhao
    • , Ganiraju C. Manyam
    • , Li Zhang
    • , Kimberly Schluns
    • , Pingwei Li
    • , Jing Wang
    •  & Shao-Cong Sun
  • Article |

    Many tumors evade immunosurveillance by down-modulating expression of antigen-processing machinery and MHC molecules. Yang et al. report triple-negative tumor cell expression of the lncRNA LINK-A enhances degradation of antigen peptide-loading complex molecules and intrinsic tumor suppressors, which contribute to tumor persistence.

    • Qingsong Hu
    • , Youqiong Ye
    • , Li-Chuan Chan
    • , Yajuan Li
    • , Ke Liang
    • , Aifu Lin
    • , Sergey D. Egranov
    • , Yaohua Zhang
    • , Weiya Xia
    • , Jing Gong
    • , Yinghong Pan
    • , Sujash S. Chatterjee
    • , Jun Yao
    • , Kurt W. Evans
    • , Tina K. Nguyen
    • , Peter K. Park
    • , Jiewei Liu
    • , Cristian Coarfa
    • , Sri Ramya Donepudi
    • , Vasanta Putluri
    • , Nagireddy Putluri
    • , Arun Sreekumar
    • , Chandrashekar R. Ambati
    • , David H. Hawke
    • , Jeffrey R. Marks
    • , Preethi H. Gunaratne
    • , Abigail S. Caudle
    • , Aysegul A. Sahin
    • , Gabriel N. Hortobagyi
    • , Funda Meric-Bernstam
    • , Lieping Chen
    • , Dihua Yu
    • , Mien-Chie Hung
    • , Michael A. Curran
    • , Leng Han
    • , Chunru Lin
    •  & Liuqing Yang
  • Article |

    High-energy diet triggers mild β cell proliferation to compensate for peripheral insulin resistance. Qi and colleagues show that TLR2 and TLR4 inhibit the diet-induced replication of β cells in mice and humans.

    • Yewei Ji
    • , Shengyi Sun
    • , Neha Shrestha
    • , Laurel B. Darragh
    • , Jun Shirakawa
    • , Yuan Xing
    • , Yi He
    • , Bethany A. Carboneau
    • , Hana Kim
    • , Duo An
    • , Minglin Ma
    • , Jose Oberholzer
    • , Scott A. Soleimanpour
    • , Maureen Gannon
    • , Chengyang Liu
    • , Ali Naji
    • , Rohit N. Kulkarni
    • , Yong Wang
    • , Sander Kersten
    •  & Ling Qi
  • Article |

    Cachexia manifests in cancer, chronic inflammation and infections. Bergthaler and colleagues show that CD8+ T cells mediate infection-associated cachexia in a manner dependent on T cell–intrinsic type I IFN signaling and antigen recognition.

    • Hatoon Baazim
    • , Martina Schweiger
    • , Michael Moschinger
    • , Haifeng Xu
    • , Thomas Scherer
    • , Alexandra Popa
    • , Suchira Gallage
    • , Adnan Ali
    • , Kseniya Khamina
    • , Lindsay Kosack
    • , Bojan Vilagos
    • , Mark Smyth
    • , Alexander Lercher
    • , Joachim Friske
    • , Doron Merkler
    • , Alan Aderem
    • , Thomas H. Helbich
    • , Mathias Heikenwälder
    • , Philipp A. Lang
    • , Rudolf Zechner
    •  & Andreas Bergthaler
  • Article |

    Edelson and colleagues show that the transcription factor Bhlhe40 is required in a cell-intrinsic manner for the self-renewal and maintenance of large peritoneal macrophages, but not that of other tissue-resident macrophages.

    • Nicholas N. Jarjour
    • , Elizabeth A. Schwarzkopf
    • , Tara R. Bradstreet
    • , Irina Shchukina
    • , Chih-Chung Lin
    • , Stanley Ching-Cheng Huang
    • , Chin-Wen Lai
    • , Melissa E. Cook
    • , Reshma Taneja
    • , Thaddeus S. Stappenbeck
    • , Gwendalyn J. Randolph
    • , Maxim N. Artyomov
    • , Joseph F. Urban Jr
    •  & Brian T. Edelson
  • Article |

    HIV-1 target cells employ a number of factors that restrict the production of viral progeny. Liang and colleagues identify the cell membrane-localized metalloprotease TRABD2A as a previously unknown restriction factor that acts at the late phase of infection to degrade HIV-1 Gag polyprotein.

    • Guoxin Liang
    • , Li Zhao
    • , Ying Qiao
    • , Wenqing Geng
    • , Xiaowei Zhang
    • , Mei Liu
    • , Jinxiu Dong
    • , Haibo Ding
    • , Hong Sun
    •  & Hong Shang
  • Article |

    BCR signaling in naive B cells and in GC B cells differs. Shlomchik and colleagues report that GC B cells are ‘rewired’ in their Akt activation module, increasing p-T308 over p-S473, leading to increases of negative regulators of BCR signaling and ultimately higher thresholds for BCR activation.

    • Wei Luo
    • , William Hawse
    • , Laura Conter
    • , Nikita Trivedi
    • , Florian Weisel
    • , Daniel Wikenheiser
    • , Richard T. Cattley
    •  & Mark J. Shlomchik
  • Article |

    Innate immunity protects the central nervous system against fungal pathogens. Lionakis and colleagues identify Candidalysin, a Candida virulence factor that elicits microglial expression of the cytokine IL-1β and chemokine CXCL1 and facilitates neutrophil recruitment. Alteration of this pathway impairs antifungal responses.

    • Rebecca A. Drummond
    • , Muthulekha Swamydas
    • , Vasileios Oikonomou
    • , Bing Zhai
    • , Ivy M. Dambuza
    • , Brian C. Schaefer
    • , Andrea C. Bohrer
    • , Katrin D. Mayer-Barber
    • , Sergio A. Lira
    • , Yoichiro Iwakura
    • , Scott G. Filler
    • , Gordon D. Brown
    • , Bernhard Hube
    • , Julian R. Naglik
    • , Tobias M. Hohl
    •  & Michail S. Lionakis
  • Article |

    Succinate is a signaling metabolite sensed extracellularly by SUNCR1. Fernandez-Veledo and colleagues show that activation of SUCNR1 promotes an anti-inflammatory phenotype in adipose-tissue macrophages in lean mice and people.

    • Noelia Keiran
    • , Victoria Ceperuelo-Mallafré
    • , Enrique Calvo
    • , Maria Isabel Hernández-Alvarez
    • , Miriam Ejarque
    • , Catalina Núñez-Roa
    • , Daniel Horrillo
    • , Elsa Maymó-Masip
    • , M. Mar Rodríguez
    • , Rosa Fradera
    • , Juan Vladimir de la Rosa
    • , Rosa Jorba
    • , Ana Megia
    • , Antonio Zorzano
    • , Gema Medina-Gómez
    • , Carolina Serena
    • , Antonio Castrillo
    • , Joan Vendrell
    •  & Sonia Fernández-Veledo
  • Article |

    Fibroblastic reticular cells support lymph-node function and adaptive immunity. McGeachy and colleagues show that the cytokine IL-17 is needed to trigger metabolic changes required for the proliferation and survival of these cells in reactive lymph nodes.

    • Saikat Majumder
    • , Nilesh Amatya
    • , Shankar Revu
    • , Chetan V. Jawale
    • , Dongwen Wu
    • , Natalie Rittenhouse
    • , Ashley Menk
    • , Saran Kupul
    • , Fang Du
    • , Itay Raphael
    • , Amrita Bhattacharjee
    • , Ulrich Siebenlist
    • , Timothy W. Hand
    • , Greg M. Delgoffe
    • , Amanda C. Poholek
    • , Sarah L. Gaffen
    • , Partha S. Biswas
    •  & Mandy J. McGeachy
  • Article |

    Regulatory T cells obstruct effective anti-cancer immune responses. Vignali and colleagues demonstrate that IL-10 production and IL-35 production by tumor-infiltrating regulatory T cells mediate differential and non-redundant suppressive effects on tumor-reactive cytotoxic T cells.

    • Deepali V. Sawant
    • , Hiroshi Yano
    • , Maria Chikina
    • , Qianxia Zhang
    • , Mengting Liao
    • , Chang Liu
    • , Derrick J. Callahan
    • , Zhe Sun
    • , Tao Sun
    • , Tracy Tabib
    • , Arjun Pennathur
    • , David B. Corry
    • , James D. Luketich
    • , Robert Lafyatis
    • , Wei Chen
    • , Amanda C. Poholek
    • , Tullia C. Bruno
    • , Creg J. Workman
    •  & Dario A. A. Vignali
  • Article |

    Control of macrophage activation in the lungs is essential for the prevention of tissue damage. MacDonald and colleagues show that alveolar macrophages have impaired glycolysis and are hyporesponsive during type 2 inflammation in a manner controlled by the lung environment.

    • Freya R. Svedberg
    • , Sheila L. Brown
    • , Maria Z. Krauss
    • , Laura Campbell
    • , Catherine Sharpe
    • , Maryam Clausen
    • , Gareth J. Howell
    • , Howard Clark
    • , Jens Madsen
    • , Christopher M. Evans
    • , Tara E. Sutherland
    • , Alasdair C. Ivens
    • , David J. Thornton
    • , Richard K. Grencis
    • , Tracy Hussell
    • , Danen M. Cunoosamy
    • , Peter C. Cook
    •  & Andrew S. MacDonald
  • Article |

    Neutrophils rapidly respond to bacterial and fungal infections but can cause substantial collateral tissue damage if not restrained. Rosenbauer and colleagues show that the transcription factor PU.1 serves a cell-intrinsic role to prevent over-exuberant neutrophil responses to fungal infection.

    • Josephine Fischer
    • , Carolin Walter
    • , Alexander Tönges
    • , Hanna Aleth
    • , Marta Joana Costa Jordão
    • , Mathias Leddin
    • , Verena Gröning
    • , Tabea Erdmann
    • , Georg Lenz
    • , Johannes Roth
    • , Thomas Vogl
    • , Marco Prinz
    • , Martin Dugas
    • , Ilse D. Jacobsen
    •  & Frank Rosenbauer
  • Article |

    The cytokine IL-6 controls the survival, proliferation and effector functions of lymphocytes. Jones and colleagues show that activation of CD4+ T cells leads to suppression of STAT1 activation by tyrosine phosphatases and changes the effector characteristics of memory CD4+ T cells in response to IL-6.

    • Jason P. Twohig
    • , Ana Cardus Figueras
    • , Robert Andrews
    • , Florian Wiede
    • , Benjamin C. Cossins
    • , Alicia Derrac Soria
    • , Myles J. Lewis
    • , Michael J. Townsend
    • , David Millrine
    • , Jasmine Li
    • , David G. Hill
    • , Javier Uceda Fernandez
    • , Xiao Liu
    • , Barbara Szomolay
    • , Christopher J. Pepper
    • , Philip R. Taylor
    • , Costantino Pitzalis
    • , Tony Tiganis
    • , Nigel M. Williams
    • , Gareth W. Jones
    •  & Simon A. Jones
  • Article |

    The role of IFN-λ in adaptive immunity is not well characterized. Staeheli and colleagues show that in the lungs, IFN-λ elicits production of the cytokine TSLP from M cells and that this in turn is essential for effective adaptive immunity and control of infection with influenza virus.

    • Liang Ye
    • , Daniel Schnepf
    • , Jan Becker
    • , Karolina Ebert
    • , Yakup Tanriver
    • , Valentina Bernasconi
    • , Hans Henrik Gad
    • , Rune Hartmann
    • , Nils Lycke
    •  & Peter Staeheli
  • Article |

    The central nervous system meninges have a dense network of yolk sac–derived macrophages that serve a sentinel role. McGavern and colleagues show that this meningeal niche is replenished by bone marrow–derived inflammatory monocytes, which alters meningeal immune reactions after subsequent immune challenge.

    • Rejane Rua
    • , Jane Y. Lee
    • , Alexander B. Silva
    • , Isabella S. Swafford
    • , Dragan Maric
    • , Kory R. Johnson
    •  & Dorian B. McGavern
  • Article |

    Lymph fluid carries cells, debris and viruses to draining lymph nodes. Hickman and colleagues show that large viruses can enter lymph node conduits and gain access to dendritic cells positioned deep within lymph nodes for efficient presentation of antigen to CD8+ T cells.

    • Glennys V. Reynoso
    • , Andrea S. Weisberg
    • , John P. Shannon
    • , Daniel T. McManus
    • , Lucas Shores
    • , Jeffrey L. Americo
    • , Radu V. Stan
    • , Jonathan W. Yewdell
    •  & Heather D. Hickman
  • Article |

    Macrophages can shift their cellular metabolism in response to tissue cues and infection. Pearce and colleagues show that lipopolysaccharide-activated ‘inflammatory’ macrophages become depleted of NAD+ pools and require the salvage-pathway enzyme NAMPT to sustain cellular redox balance.

    • Alanna M. Cameron
    • , Angela Castoldi
    • , David E. Sanin
    • , Lea J. Flachsmann
    • , Cameron S. Field
    • , Daniel. J. Puleston
    • , Ryan L. Kyle
    • , Annette E. Patterson
    • , Fabian Hässler
    • , Joerg M. Buescher
    • , Beth Kelly
    • , Erika L. Pearce
    •  & Edward J. Pearce
  • Article |

    Shulman and colleagues show that in contrast to events in lymph nodes and spleen, in Peyer’s patches, T cells promote B cell expansion without clonal selection during pre-germinal center events.

    • Adi Biram
    • , Anneli Strömberg
    • , Eitan Winter
    • , Liat Stoler-Barak
    • , Ran Salomon
    • , Yoseph Addadi
    • , Rony Dahan
    • , Gur Yaari
    • , Mats Bemark
    •  & Ziv Shulman
  • Article |

    Removal of damaged mitochondria maintains cellular homeostasis and regulates inflammation. Qian and colleagues describe a mechanism by which intracellular bacteria such as Listeria can elicit mitophagy to enable their survival.

    • Yifan Zhang
    • , Yikun Yao
    • , Xiaoxu Qiu
    • , Guodong Wang
    • , Zheng Hu
    • , Siyuan Chen
    • , Zhengxi Wu
    • , Na Yuan
    • , Hanchao Gao
    • , Jianrong Wang
    • , Houhui Song
    • , Stephen E. Girardin
    •  & Youcun Qian
  • Article |

    Eosinophils have been described mainly in allergy settings but are increasingly appreciated as being involved in other aspects of immunity. Albert and colleagues use a clinically approved inhibitor of the dipeptidyl peptidase DPP4 to facilitate the recruitment of eosinophils to mouse tumors, where they are essential in tumor destruction.

    • Clémence Hollande
    • , Jeremy Boussier
    • , James Ziai
    • , Tamaki Nozawa
    • , Vincent Bondet
    • , Wilson Phung
    • , Binfeng Lu
    • , Darragh Duffy
    • , Valerie Paradis
    • , Vincent Mallet
    • , Gérard Eberl
    • , Wendy Sandoval
    • , Jill M. Schartner
    • , Stanislas Pol
    • , Rosa Barreira da Silva
    •  & Matthew L. Albert
  • Article |

    Exhausted cytotoxic T lymphocytes (CTLs) express the receptor PD-1 as a key signature. Haining and colleagues show that there are different ‘depths’ of exhaustion with a subset of exhausted CTLs that retain polyfunctionality and are responsive to PD-1 blockade.

    • Brian C. Miller
    • , Debattama R. Sen
    • , Rose Al Abosy
    • , Kevin Bi
    • , Yamini V. Virkud
    • , Martin W. LaFleur
    • , Kathleen B. Yates
    • , Ana Lako
    • , Kristen Felt
    • , Girish S. Naik
    • , Michael Manos
    • , Evisa Gjini
    • , Juhi R. Kuchroo
    • , Jeffrey J. Ishizuka
    • , Jenna L. Collier
    • , Gabriel K. Griffin
    • , Seth Maleri
    • , Dawn E. Comstock
    • , Sarah A. Weiss
    • , Flavian D. Brown
    • , Arpit Panda
    • , Margaret D. Zimmer
    • , Robert T. Manguso
    • , F. Stephen Hodi
    • , Scott J. Rodig
    • , Arlene H. Sharpe
    •  & W. Nicholas Haining
  • Article |

    Stemness is crucial for the maintenance of long-term T cell memory. Gattinoni and colleagues demonstrate that the transcription factor c-Myb is essential for the establishment of a stemness program in the CD8+ T cell memory compartment.

    • Sanjivan Gautam
    • , Jessica Fioravanti
    • , Wei Zhu
    • , John B. Le Gall
    • , Philip Brohawn
    • , Neal E. Lacey
    • , Jinhui Hu
    • , James D. Hocker
    • , Nga Voong Hawk
    • , Veena Kapoor
    • , William G. Telford
    • , Devikala Gurusamy
    • , Zhiya Yu
    • , Avinash Bhandoola
    • , Hai-Hui Xue
    • , Rahul Roychoudhuri
    • , Brandon W. Higgs
    • , Nicholas P. Restifo
    • , Timothy P. Bender
    • , Yun Ji
    •  & Luca Gattinoni
  • Article |

    Cross-protective responses across all strains of influenza virus (IAV, IBV and ICV) are a key goal of universal vaccines against influenza. Kedzierska and colleagues identify cytotoxic T cells present in blood and lungs of healthy people that are directed against all strains of influenza virus.

    • Marios Koutsakos
    • , Patricia T. Illing
    • , Thi H. O. Nguyen
    • , Nicole A. Mifsud
    • , Jeremy Chase Crawford
    • , Simone Rizzetto
    • , Auda A. Eltahla
    • , E. Bridie Clemens
    • , Sneha Sant
    • , Brendon Y. Chua
    • , Chinn Yi Wong
    • , E. Kaitlynn Allen
    • , Don Teng
    • , Pradyot Dash
    • , David F. Boyd
    • , Ludivine Grzelak
    • , Weiguang Zeng
    • , Aeron C. Hurt
    • , Ian Barr
    • , Steve Rockman
    • , David C. Jackson
    • , Tom C. Kotsimbos
    • , Allen C. Cheng
    • , Michael Richards
    • , Glen P. Westall
    • , Thomas Loudovaris
    • , Stuart I. Mannering
    • , Michael Elliott
    • , Stuart G. Tangye
    • , Linda M. Wakim
    • , Jamie Rossjohn
    • , Dhanasekaran Vijaykrishna
    • , Fabio Luciani
    • , Paul G. Thomas
    • , Stephanie Gras
    • , Anthony W. Purcell
    •  & Katherine Kedzierska
  • Article |

    An intricately linked homeostasis exists between the gut microbiome and host immune system. Scheffold and colleagues show that intestinal Treg cells upregulate the transcription factor c-Maf in response to specific signals from the gut microenvironment to establish host–microbiota homeostasis.

    • Christian Neumann
    • , Jonas Blume
    • , Urmi Roy
    • , Peggy P. Teh
    • , Ajithkumar Vasanthakumar
    • , Alexander Beller
    • , Yang Liao
    • , Frederik Heinrich
    • , Teresita L. Arenzana
    • , Jason A. Hackney
    • , Celine Eidenschenk
    • , Eric J. C. Gálvez
    • , Christina Stehle
    • , Gitta A. Heinz
    • , Patrick Maschmeyer
    • , Tom Sidwell
    • , Yifang Hu
    • , Derk Amsen
    • , Chiara Romagnani
    • , Hyun-Dong Chang
    • , Andrey Kruglov
    • , Mir-Farzin Mashreghi
    • , Wei Shi
    • , Till Strowig
    • , Sascha Rutz
    • , Axel Kallies
    •  & Alexander Scheffold
  • Article |

    Antigenic variation of influenza A viruses necessitates the annual reformulation of vaccines. Kanekiyo et al. develop a mosaic nanoparticle vaccine against influenza virus that is able to elicit neutralizing antibodies that span nearly 100 years of variation of influenza A virus.

    • Masaru Kanekiyo
    • , M. Gordon Joyce
    • , Rebecca A. Gillespie
    • , John R. Gallagher
    • , Sarah F. Andrews
    • , Hadi M. Yassine
    • , Adam K. Wheatley
    • , Brian E. Fisher
    • , David R. Ambrozak
    • , Adrian Creanga
    • , Kwanyee Leung
    • , Eun Sung Yang
    • , Seyhan Boyoglu-Barnum
    • , Ivelin S. Georgiev
    • , Yaroslav Tsybovsky
    • , Madhu S. Prabhakaran
    • , Hanne Andersen
    • , Wing-Pui Kong
    • , Ulrich Baxa
    • , Kathryn L. Zephir
    • , Julie E. Ledgerwood
    • , Richard A. Koup
    • , Peter D. Kwong
    • , Audray K. Harris
    • , Adrian B. McDermott
    • , John R. Mascola
    •  & Barney S. Graham
  • Article |

    Pathogenic human CD4+ T cells in rheumatoid arthritis have hyperactivated metabolism. Weyand and colleagues show that this phenotype is associated with less myristoylation of the energy sensor AMPK and dysregulated metabolic sensor mTORC1.

    • Zhenke Wen
    • , Ke Jin
    • , Yi Shen
    • , Zhen Yang
    • , Yinyin Li
    • , Bowen Wu
    • , Lu Tian
    • , Stanford Shoor
    • , Niall E. Roche
    • , Jorg J. Goronzy
    •  & Cornelia M. Weyand
  • Article |

    Zinc is important for normal immunity but its mechanistic actions are poorly understood. Hambleton and colleagues identify defects in Zn2+ transport that underpin a novel human immunodeficiency characterized by loss of mature B cells.

    • Consuelo Anzilotti
    • , David J. Swan
    • , Bertrand Boisson
    • , Mukta Deobagkar-Lele
    • , Catarina Oliveira
    • , Pauline Chabosseau
    • , Karin R. Engelhardt
    • , Xijin Xu
    • , Rui Chen
    • , Luis Alvarez
    • , Rolando Berlinguer-Palmini
    • , Katherine R. Bull
    • , Eleanor Cawthorne
    • , Adam P. Cribbs
    • , Tanya L. Crockford
    • , Tarana Singh Dang
    • , Amy Fearn
    • , Emma J. Fenech
    • , Sarah J. de Jong
    • , B. Christoffer Lagerholm
    • , Cindy S. Ma
    • , David Sims
    • , Bert van den Berg
    • , Yaobo Xu
    • , Andrew J. Cant
    • , Gary Kleiner
    • , T. Ronan Leahy
    • , M. Teresa de la Morena
    • , Jennifer M. Puck
    • , Ralph S. Shapiro
    • , Mirjam van der Burg
    • , J. Ross Chapman
    • , John C. Christianson
    • , Benjamin Davies
    • , John A. McGrath
    • , Stefan Przyborski
    • , Mauro Santibanez Koref
    • , Stuart G. Tangye
    • , Andreas Werner
    • , Guy A. Rutter
    • , Sergi Padilla-Parra
    • , Jean-Laurent Casanova
    • , Richard J. Cornall
    • , Mary Ellen Conley
    •  & Sophie Hambleton
  • Article |

    Serpins are a large family of serine protease inhibitors. Jae Jung and colleagues show that SERPINB1 serves an endogenous regulatory role for pro-inflammatory caspases by preventing CARD–CARD polymerization and, hence, inflammasome activation.

    • Youn Jung Choi
    • , Stephanie Kim
    • , Younho Choi
    • , Travis B. Nielsen
    • , Jun Yan
    • , Alvin Lu
    • , Jianbin Ruan
    • , Hye-Ra Lee
    • , Hao Wu
    • , Brad Spellberg
    •  & Jae U. Jung
  • Article |

    Tissue-resident memory T cells (TRM cells) have well-described functions in the protective response to infectious agents. Neurath and colleagues demonstrate that intestinal TRM cells can also have key pathogenic roles in inflammatory bowel disease.

    • Sebastian Zundler
    • , Emily Becker
    • , Marta Spocinska
    • , Monique Slawik
    • , Loreto Parga-Vidal
    • , Regina Stark
    • , Maximilian Wiendl
    • , Raja Atreya
    • , Timo Rath
    • , Moritz Leppkes
    • , Kai Hildner
    • , Rocío López-Posadas
    • , Sören Lukassen
    • , Arif B. Ekici
    • , Clemens Neufert
    • , Imke Atreya
    • , Klaas P. J. M. van Gisbergen
    •  & Markus F. Neurath
  • Article |

    Koning and colleagues used mass cytometry, single-cell RNA-seq and high-throughput TCR sequencing to characterize the CD4+ T cell compartment in the human fetal intestine.

    • Na Li
    • , Vincent van Unen
    • , Tamim Abdelaal
    • , Nannan Guo
    • , Sofya A. Kasatskaya
    • , Kristin Ladell
    • , James E. McLaren
    • , Evgeny S. Egorov
    • , Mark Izraelson
    • , Susana M. Chuva de Sousa Lopes
    • , Thomas Höllt
    • , Olga V Britanova
    • , Jeroen Eggermont
    • , Noel F. C. C. de Miranda
    • , Dmitriy M. Chudakov
    • , David A. Price
    • , Boudewijn P. F. Lelieveldt
    •  & Frits Koning
  • Article |

    Basophils constitute <1% of peripheral blood leukocytes. Piliponsky and colleagues show that basophils serve as a critical component of antibacterial responses by secreting tumor necrosis factor at early time points after systemic infection.

    • Adrian M. Piliponsky
    • , Nicholas J. Shubin
    • , Asha K. Lahiri
    • , Phuong Truong
    • , Morgan Clauson
    • , Kerri Niino
    • , Avery L. Tsuha
    • , Sergei A. Nedospasov
    • , Hajime Karasuyama
    • , Laurent L. Reber
    • , Mindy Tsai
    • , Kaori Mukai
    •  & Stephen J. Galli
  • Article |

    Macrophages have important antitumor functions but can be evaded by tumor-expressed CD47-dependent ‘don’t-eat-me’ signals. Beatty and colleagues demonstrate that the Toll-like receptor 9 ligand CpG metabolically reprograms macrophages to overcome don’t-eat-me signals.

    • Mingen Liu
    • , Roddy S. O’Connor
    • , Sophie Trefely
    • , Kathleen Graham
    • , Nathaniel W. Snyder
    •  & Gregory L. Beatty
  • Article |

    The tumor microenvironment is central to the immunogenicity of tumors. Ho and colleagues show that activity of the mitochondrial protein UCP2 in tumors enhances their immunogenicity through the recruitment of dendritic cells and reprogramming of this microenvironment.

    • Wan-Chen Cheng
    • , Yao-Chen Tsui
    • , Simone Ragusa
    • , Viktor H. Koelzer
    • , Marco Mina
    • , Fabien Franco
    • , Heinz Läubli
    • , Benjamin Tschumi
    • , Daniel Speiser
    • , Pedro Romero
    • , Alfred Zippelius
    • , Tatiana V. Petrova
    • , Kirsten Mertz
    • , Giovanni Ciriello
    •  & Ping-Chih Ho