Browse Articles

  • Review Article |

    Underlying inflammatory bowel disease is a complex web of activated immune cells. In this Review, Neurath delineates the cells, pathways and signals that contribute to the pathology of inflammatory bowel disease and the potential for therapeutic intervention.

    • Markus F. Neurath
  • 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
  • Editorial |

    Adaptive behaviors in hematopoietic cells can promote homeostasis and enhance immune responses to pathogens, but they can also perpetuate the chronicity of inflammatory or metabolic disorders.

  • Review Article |

    In this Review, Pearce and colleagues discuss the metabolic adaptation of immune cells to various tissues and how functional adaptation compared with maladaptation within the niche can affect tissue homeostasis.

    • George Caputa
    • , Angela Castoldi
    •  & Edward J. Pearce
  • Review Article |

    In this Review, Natoli and Ostuni discuss the mechanisms of adaptation and memory in immunity, with the aim of providing basic concepts that rationalize the properties and molecular bases of these essential processes.

    • Gioacchino Natoli
    •  & Renato Ostuni
  • 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
  • News & Views |

    Novel single-cell profiling technologies have delineated the cellular and molecular landscapes that dominate the joints in rheumatoid arthritis and the skin and kidneys in systemic lupus erythematosus, shedding light on potential pathogenic mechanisms.

    • Navin Varadarajan
    •  & Chandra Mohan
  • 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
  • News & Views |

    Although the molecular basis of most disease-associated single-nucleotide polymorphisms has remained elusive, an HIV-1 viral load–associated polymorphism (rs1015164) has been identified that marks expression of a long non-coding RNA that regulates the co-receptor CCR5 and thereby influences infection of CD4+ T cells.

    • Sanath Kumar Janaka
    •  & David T. Evans
  • 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
  • Resource |

    Much about the kidney-resident immune populations is a black box. Hacohen and colleagues use single cell RNA sequencing of kidney, skin and urine from lupus nephritis patients to describe the transcriptional state of the immune cells present in each compartment.

    • Arnon Arazi
    • , Deepak A. Rao
    • , Celine C. Berthier
    • , Anne Davidson
    • , Yanyan Liu
    • , Paul J. Hoover
    • , Adam Chicoine
    • , Thomas M. Eisenhaure
    • , A. Helena Jonsson
    • , Shuqiang Li
    • , David J. Lieb
    • , Fan Zhang
    • , Kamil Slowikowski
    • , Edward P. Browne
    • , Akiko Noma
    • , Danielle Sutherby
    • , Scott Steelman
    • , Dawn E. Smilek
    • , Patti Tosta
    • , William Apruzzese
    • , Elena Massarotti
    • , Maria Dall’Era
    • , Meyeon Park
    • , Diane L. Kamen
    • , Richard A. Furie
    • , Fernanda Payan-Schober
    • , William F. Pendergraft III
    • , Elizabeth A. McInnis
    • , Jill P. Buyon
    • , Michelle A. Petri
    • , Chaim Putterman
    • , Kenneth C. Kalunian
    • , E. Steve Woodle
    • , James A. Lederer
    • , David A. Hildeman
    • , Chad Nusbaum
    • , Soumya Raychaudhuri
    • , Matthias Kretzler
    • , Jennifer H. Anolik
    • , Michael B. Brenner
    • , David Wofsy
    • , Nir Hacohen
    • , Betty Diamond
    • , Arnon Arazi
    • , Deepak A. Rao
    • , Celine C. Berthier
    • , Anne Davidson
    • , Yanyan Liu
    • , Paul J. Hoover
    • , Adam Chicoine
    • , Thomas M. Eisenhaure
    • , A. Helena Jonsson
    • , Shuqiang Li
    • , David J. Lieb
    • , Fan Zhang
    • , Kamil Slowikowski
    • , Edward P. Browne
    • , Akiko Noma
    • , Danielle Sutherby
    • , Scott Steelman
    • , Dawn E. Smilek
    • , Patti Tosta
    • , William Apruzzese
    • , Elena Massarotti
    • , Maria Dall’Era
    • , Meyeon Park
    • , Diane L. Kamen
    • , Richard A. Furie
    • , Fernanda Payan-Schober
    • , William F. Pendergraft III
    • , Elizabeth A. McInnis
    • , Jill P. Buyon
    • , Michelle A. Petri
    • , Chaim Putterman
    • , Kenneth C. Kalunian
    • , E. Steve Woodle
    • , James A. Lederer
    • , David A. Hildeman
    • , Chad Nusbaum
    • , Soumya Raychaudhuri
    • , Matthias Kretzler
    • , Jennifer H. Anolik
    • , Michael B. Brenner
    • , David Wofsy
    • , Nir Hacohen
    • , Betty Diamond
    • , Dia Waguespack
    • , Sean M. Connery
    • , Maureen A. McMahon
    • , William J. McCune
    • , Ruba B. Kado
    • , Raymond Hsu
    • , Melissa A. Cunningham
    • , Paul J. Utz
    • , Mina Pichavant
    • , Holden T. Maecker
    • , Rohit Gupta
    • , Judith A. James
    • , Joel M. Guthridge
    • , Chamith Fonseka
    • , Evan Der
    • , Robert Clancy
    • , Thomas Tuschl
    • , Hemant Suryawanshi
    • , Andrea Fava
    •  & Daniel H. Goldman
  • 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
  • News & Views |

    The cytokine IL-15 controls the homeostasis and activation of CD8+ T cells and natural killer cells. A new study reveals the deubiquitinase Otub1 to be a negative regulator of IL-15 signaling, with important consequences for autoimmunity and anti-cancer immunity.

    • Paul N. Moynagh
  • Comment |

    On 18 December 2018, the National Institute of Allergy and Infectious Diseases convened a workshop entitled ‘Recent Advances and Opportunities in the Development and Use of Humanized Immune System Mouse Models’.

    • Todd M. Allen
    • , Michael A. Brehm
    • , Sandra Bridges
    • , Stacy Ferguson
    • , Priti Kumar
    • , Oleg Mirochnitchenko
    • , Karolina Palucka
    • , Roberta Pelanda
    • , Brigitte Sanders-Beer
    • , Leonard D. Shultz
    • , Lishan Su
    •  & Mercy PrabhuDas
  • 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
  • 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