Browse Articles

  • Technical Report |

    Tissue-resident memory T (TRM) cells have been studied mainly in mouse models. Schumacher and colleagues have developed an imaging technology to track in real time skin-resident human CD8+ TRM cells in situ.

    • Feline E. Dijkgraaf
    • , Tiago R. Matos
    • , Mark Hoogenboezem
    • , Mireille Toebes
    • , David W. Vredevoogd
    • , Marjolijn Mertz
    • , Bram van den Broek
    • , Ji-Ying Song
    • , Marcel B. M. Teunissen
    • , Rosalie M. Luiten
    • , Joost B. Beltman
    •  & Ton N. Schumacher
  • 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
  • Resource |

    Nephritis is a major cause of lupus morbidity. Putterman and colleagues use single-cell RNA sequencing on human renal and skin biopsies to describe the expression landscape associated with lupus nephritis.

    • Evan Der
    • , Hemant Suryawanshi
    • , Pavel Morozov
    • , Manjunath Kustagi
    • , Beatrice Goilav
    • , Saritha Ranabathou
    • , Peter Izmirly
    • , Robert Clancy
    • , H. Michael Belmont
    • , Mordecai Koenigsberg
    • , Michele Mokrzycki
    • , Helen Rominieki
    • , Jay A. Graham
    • , Juan P. Rocca
    • , Nicole Bornkamp
    • , Nicole Jordan
    • , Emma Schulte
    • , Ming Wu
    • , James Pullman
    • , Kamil Slowikowski
    • , Soumya Raychaudhuri
    • , Joel Guthridge
    • , Judith James
    • , Jill Buyon
    • , Thomas Tuschl
    • , Chaim Putterman
    • , Jennifer Anolik
    • , William Apruzzese
    • , Arnon Arazi
    • , Celine Berthier
    • , Michael Brenner
    • , Jill Buyon
    • , Robert Clancy
    • , Sean Connery
    • , Melissa Cunningham
    • , Maria Dall’Era
    • , Anne Davidson
    • , Evan Der
    • , Andrea Fava
    • , Chamith Fonseka
    • , Richard Furie
    • , Dan Goldman
    • , Rohit Gupta
    • , Joel Guthridge
    • , Nir Hacohen
    • , David Hildeman
    • , Paul Hoover
    • , Raymond Hsu
    • , Judith James
    • , Ruba Kado
    • , Kenneth Kalunian
    • , Diane Kamen
    • , Mattias Kretzler
    • , Holden Maecker
    • , Elena Massarotti
    • , William McCune
    • , Maureen McMahon
    • , Meyeon Park
    • , Fernanda Payan-Schober
    • , William Pendergraft
    • , Michelle Petri
    • , Mina Pichavant
    • , Chaim Putterman
    • , Deepak Rao
    • , Soumya Raychaudhuri
    • , Kamil Slowikowski
    • , Hemant Suryawanshi
    • , Thomas Tuschl
    • , Paul Utz
    • , Dia Waguespack
    • , David Wofsy
    •  & Fan Zhang
  • 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
  • Resource |

    Defining cell types and their activation status in rheumatoid arthritis (RA) is critical to understanding this disease. Raychaudhuri and colleagues leverage several single-cell -omics approaches to define the cellular processes and pathways in the human RA joint.

    • Fan Zhang
    • , Kevin Wei
    • , Kamil Slowikowski
    • , Chamith Y. Fonseka
    • , Deepak A. Rao
    • , Stephen Kelly
    • , Susan M. Goodman
    • , Darren Tabechian
    • , Laura B. Hughes
    • , Karen Salomon-Escoto
    • , Gerald F. M. Watts
    • , A. Helena Jonsson
    • , Javier Rangel-Moreno
    • , Nida Meednu
    • , Cristina Rozo
    • , William Apruzzese
    • , Thomas M. Eisenhaure
    • , David J. Lieb
    • , David L. Boyle
    • , Arthur M. Mandelin II
    • , Jennifer Albrecht
    • , S. Louis Bridges Jr.
    • , Christopher D. Buckley
    • , Jane H. Buckner
    • , James Dolan
    • , Joel M. Guthridge
    • , Maria Gutierrez-Arcelus
    • , Lionel B. Ivashkiv
    • , Eddie A. James
    • , Judith A. James
    • , Josh Keegan
    • , Yvonne C. Lee
    • , Mandy J. McGeachy
    • , Michael A. McNamara
    • , Joseph R. Mears
    • , Fumitaka Mizoguchi
    • , Jennifer P. Nguyen
    • , Akiko Noma
    • , Dana E. Orange
    • , Mina Rohani-Pichavant
    • , Christopher Ritchlin
    • , William H. Robinson
    • , Anupamaa Seshadri
    • , Danielle Sutherby
    • , Jennifer Seifert
    • , Jason D. Turner
    • , Paul J. Utz
    • , Brendan F. Boyce
    • , Edward DiCarlo
    • , Ellen M. Gravallese
    • , Peter K. Gregersen
    • , Larry Moreland
    • , Gary S. Firestein
    • , Nir Hacohen
    • , Chad Nusbaum
    • , James A. Lederer
    • , Harris Perlman
    • , Costantino Pitzalis
    • , Andrew Filer
    • , V. Michael Holers
    • , Vivian P. Bykerk
    • , Laura T. Donlin
    • , Jennifer H. Anolik
    • , Michael B. Brenner
    •  & Soumya Raychaudhuri
  • 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
  • News & Views |

    The transcription factor Bhlhe40 is required for the homeostatic proliferation of peritoneal macrophages and their expansion during type 2 immunity.

    • Carla V. Rothlin
    •  & Sourav Ghosh
  • News & Views |

    A novel feedback loop coordinated by germinal center–specific signaling via the kinase AKT activates negative regulators of upstream BCR signaling to attenuate responses to antigen stimulation.

    • Julie Zikherman
  • News & Views |

    Expression of the immunosuppressive cytokines IL-10 and IL-35 by tumor-infiltrating regulatory T cells drives exhaustion of intratumoral CD8+ T cells through a common pathway dependent on the transcription factor BLIMP-1.

    • Martina Damo
    •  & Nikhil S. Joshi
  • 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
  • Author Correction |

    • 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 |

    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
  • Review Article |

    Comprehensive immunity requires that cells sense intracellular pathogens. In their Review, Shao and colleagues describe mechanisms for the recognition of intracellular lipopolysaccharide and its essential role in responses to Gram-negative bacteria.

    • Vijay A. K. Rathinam
    • , Yue Zhao
    •  & Feng Shao
  • News & Views |

    The cytokine IL-17 augments metabolism in fibroblastic reticular cells in lymph nodes, which enhances their proliferation and survival to support B cell responses during autoimmunity.

    • Scott N. Mueller
  • Resource |

    Respiratory infections are the principal cause of asthma exacerbations in children. Altman and colleagues use a systems approach to describe the pathways associated with asthma exacerbations in a cohort of inner-city children.

    • Matthew C. Altman
    • , Michelle A. Gill
    • , Elizabeth Whalen
    • , Denise C. Babineau
    • , Baomei Shao
    • , Andrew H. Liu
    • , Brett Jepson
    • , Rebecca S. Gruchalla
    • , George T. O’Connor
    • , Jacqueline A. Pongracic
    • , Carolyn M. Kercsmar
    • , Gurjit K. Khurana Hershey
    • , Edward M. Zoratti
    • , Christine C. Johnson
    • , Stephen J. Teach
    • , Meyer Kattan
    • , Leonard B. Bacharier
    • , Avraham Beigelman
    • , Steve M. Sigelman
    • , Scott Presnell
    • , James E. Gern
    • , Peter J. Gergen
    • , Lisa M. Wheatley
    • , Alkis Togias
    • , William W. Busse
    •  & Daniel J. Jackson
  • News & Views |

    The transcription factor PU.1 is not needed for the maintenance of neutrophil identity but is essential for the prevention of excessive tissue damage due to a prolonged immune response. PU.1 restrains the activation of neutrophils by antagonizing the AP-1 transcription factor JunB.

    • Richard Dahl
  • 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
  • News & Views |

    The N6-methyladenosine (m6A) RNA-modification pathway affects numerous aspects of immune responses. A new study now demonstrates that m6A modification of transcripts encoding lysosomal proteases limits the efficiency of tumor-antigen cross-presentation.

    • Marianne Burbage
    • , Marine Gros
    •  & Sebastian Amigorena
  • 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
  • News & Views |

    The mechanisms by which the cytokine IFN-λ regulates adaptive immune responses are poorly understood. A new study now reveals a novel IFN-λ-mediated signal-transmission system that enhances immunity after infection of the mouse respiratory tract with influenza virus.

    • Stefan F. Wieland
    •  & Markus H. Heim
  • 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
  • Review Article |

    The skin and intestine are unique environments at the front line of the immune system. Powrie and colleagues review the distinctive adaptations acquired by regulatory T cells at these barrier surfaces.

    • Natasha Whibley
    • , Andrea Tucci
    •  & Fiona Powrie
  • 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