Featured
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Letter |
TOX is a critical regulator of tumour-specific T cell differentiation
The nuclear factor TOX is highly expressed in antigen-specific dysfunctional T cells in tumours and exhausted T cells during chronic viral infection and is a crucial regulator of the differentiation of tumour-specific T cells.
- Andrew C. Scott
- , Friederike Dündar
- & Andrea Schietinger
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Article |
TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion
The transcription factor TOX is a central regulator of the transcriptional and epigenetic development of exhausted T cells.
- Omar Khan
- , Josephine R. Giles
- & E. John Wherry
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Letter |
Brain regulatory T cells suppress astrogliosis and potentiate neurological recovery
In a mouse model of ischaemic stroke, regulatory T cells infiltrate the injured brain in response to the chemokines CCL1 and CCL20 and suppress excessive astrogliosis via the production of amphiregulin.
- Minako Ito
- , Kyoko Komai
- & Akihiko Yoshimura
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Letter |
Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity
Phenotypically, transcriptionally and metabolically diverse subsets of TH17 cells develop in a chronic autoimmune disease: one subset has inferred stemness features and low anabolic metabolism, while a reciprocal subset has higher metabolic activity that supports transdifferentiation into TH1 cells.
- Peer W. F. Karmaus
- , Xiang Chen
- & Hongbo Chi
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Letter |
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer
Tetrahydrobiopterin (BH4) is an enzyme co-factor that is involved in the nervous system; it is shown here to also function in T cell activation and proliferation, with roles in autoimmunity, allergic inflammation and cancer.
- Shane J. F. Cronin
- , Corey Seehus
- & Josef M. Penninger
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Brief Communications Arising |
Evidence that CD32a does not mark the HIV-1 latent reservoir
- Christa E. Osuna
- , So-Yon Lim
- & James B. Whitney
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Letter |
Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development
A comprehensive analysis of the thymic medulla identifies a tuft-cell-like thymic epithelial cell population that is necessary for shaping thymic function.
- Corey N. Miller
- , Irina Proekt
- & Mark S. Anderson
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Letter |
Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism
Distinct populations of lymphocytes act sequentially during development to direct maturation of the mammalian gut microbiota.
- Kairui Mao
- , Antonio P. Baptista
- & Ronald N. Germain
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Letter |
Reversing SKI–SMAD4-mediated suppression is essential for TH17 cell differentiation
TGFβ signalling regulates T helper 17 (TH17) cell differentiation by reversing SKI–SMAD4-mediated suppression of RORγt, revealing a potential therapeutic target for treating TH17-related diseases.
- Song Zhang
- , Motoki Takaku
- & Yisong Y. Wan
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Letter |
IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity
Interleukin-1 receptor 8 (IL-1R8), a negative regulator of the IL-1 family of cytokines, restrains the activity of natural killer (NK) cells, suggesting that IL-1R8 acts as a checkpoint regulator of NK cell activation and that its blockade may be of use in cancer therapy.
- Martina Molgora
- , Eduardo Bonavita
- & Alberto Mantovani
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Letter |
m6A mRNA methylation controls T cell homeostasis by targeting the IL-7/STAT5/SOCS pathways
The authors assess the role of N6-methyladenosine in T cell development and function, and show that RNA methylation controls T cell homeostasis by regulating IL-7-mediated STAT5 activation.
- Hua-Bing Li
- , Jiyu Tong
- & Richard A. Flavell
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Letter |
Identifying specificity groups in the T cell receptor repertoire
The authors devise an algorithm that can cluster T cell receptor (TCR) sequences sharing the same specificity, predict the HLA restriction of these TCR clusters on the basis of subjects’ genotypes and help to identify specific peptide major histocompatibility complex ligands.
- Jacob Glanville
- , Huang Huang
- & Mark M. Davis
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Letter |
The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition
Combined studies in MYC-driven mouse lymphomas and human Burkitt lymphoma unravel an essential role for the B-cell antigen receptor in the control of tumour B-cell fitness both in vitro and in vivo, with possible biological and clinical implications.
- Gabriele Varano
- , Simon Raffel
- & Stefano Casola
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Letter |
Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells
The chemoattractant S1P is identified as an extrinsic factor that supports naive T cell survival, and acts via a signalling mechanism to maintain mitochondrial content and function.
- Alejandra Mendoza
- , Victoria Fang
- & Susan R. Schwab
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Letter |
Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis
The authors identify in patients with rheumatoid arthritis a pathogenic subset of CD4+ T cells that augments B cell responses within inflamed tissues.
- Deepak A. Rao
- , Michael F. Gurish
- & Michael B. Brenner
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Letter |
Genome-wide in vivo screen identifies novel host regulators of metastatic colonization
Screening mutant mouse lines using a genome-wide in vivo assay identifies microenvironmental regulators of metastatic colonization and defines SPNS2 as an important mediator of lung colonization.
- Louise van der Weyden
- , Mark J. Arends
- & David J. Adams
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Article |
S-2-hydroxyglutarate regulates CD8+ T-lymphocyte fate
S-2-hydroxyglutarate produced by CD8+ T cells under hypoxic conditions affects locus-specific histone and DNA methylation patterns, which enhances T-cell proliferation, survival and recall responses.
- Petros A. Tyrakis
- , Asis Palazon
- & Randall S. Johnson
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Letter |
Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system
Hypoxia in germinal centres regulates B cell class switching via its effects on mTOR complex 1 and activation-induced cytosine deaminase activity.
- Sung Hoon Cho
- , Ariel L. Raybuck
- & Mark R. Boothby
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Letter |
EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells
The differentiation of T follicular helper cells requires the G-protein-coupled receptor Ebi2 as well as the interaction with CD25-producing dendritic cells that quench T-cell-derived interleukin-2.
- Jianhua Li
- , Erick Lu
- & Jason G. Cyster
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Letter |
Metabolic maintenance of cell asymmetry following division in activated T lymphocytes
The asymmetric distribution of mTORC1 and c-Myc in the first division of daughter cells of activated CD8 T cells affects the proliferation, metabolism and differentiation potential of their progeny.
- Katherine C. Verbist
- , Cliff S. Guy
- & Douglas R. Green
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Letter |
Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism
Modulating cholesterol metabolism can improve CD8+ T-cell-mediated immunity against tumours; genetic or pharmacological inhibition of the cholesterol esterification enzyme ACAT1 led to higher plasma membrane cholesterol levels, better T-cell receptor clustering and signalling, improved immunological synapse maturation, and enhanced antitumour activity in mice.
- Wei Yang
- , Yibing Bai
- & Chenqi Xu
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Article |
Immune homeostasis enforced by co-localized effector and regulatory T cells
Autoantigen-presenting dendritic cells are shown to interact with both effector and regulatory T cells, and effector-produced IL-2 activates the transcription factor STAT5 in regulatory T cells, which in turn upregulates suppressive molecules and prevents autoimmunity.
- Zhiduo Liu
- , Michael Y. Gerner
- & Ronald N. Germain
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Letter |
Orientation-specific joining of AID-initiated DNA breaks promotes antibody class switching
High-throughput genome-wide sequencing reveals why class switch recombination in the IgH locus, an essential step in the process of antibody generation, has a directional joining bias towards deletion rather than inversion.
- Junchao Dong
- , Rohit A. Panchakshari
- & Frederick W. Alt
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Letter |
T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection
CD8 T-cell exhaustion, although a negative prognostic indicator during persistent infections, is shown to be associated with a good outcome in autoimmune and inflammatory diseases.
- Eoin F. McKinney
- , James C. Lee
- & Kenneth G. C. Smith
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Letter |
T–B-cell entanglement and ICOSL-driven feed-forward regulation of germinal centre reaction
Interactions between T and B cells in the germinal centre are brief but involve extensive cell-surface contact in an entangled mode; ICOSL promotes T–B entanglement and B-cell acquisition of CD40L, which drives B cells to upregulate ICOSL, thus forming an intercellular feed-forward loop that is required for efficient positive selection and development of the bone marrow plasma cell compartment.
- Dan Liu
- , Heping Xu
- & Hai Qi
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Letter |
Noncoding RNA transcription targets AID to divergently transcribed loci in B cells
The 11-subunit RNA exosome is thought to regulate the mammalian noncoding transcriptome; here, a mouse model is generated in which the essential Exosc3 subunit of the RNA exosome in B cells is conditionally deleted, revealing a link between sites of genomic RNA exosome function and AID-mediated chromosomal translocations.
- Evangelos Pefanis
- , Jiguang Wang
- & Uttiya Basu
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Letter |
Transcription factor achaete-scute homologue 2 initiates follicular T-helper-cell development
Here, the helix–loop–helix transcription factor Ascl2 is shown to be critically important for the initiation of follicular T-helper-cell development and the germinal centre response.
- Xindong Liu
- , Xin Chen
- & Chen Dong
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Outlook |
Q&A: Evidence presenter
Immunologist Karolina Palucka, at the Baylor Institute for Immunology Research in Dallas, Texas, helped treat Nobel prizewinner Ralph Steinman's pancreatic cancer with dendritic cells — the cells he co-discovered. Here she explains the use of dendritic cells in cancer immunotherapy.
- Karolina Palucka
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Letter |
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
In mice, provision of butyrate—a short-chain fatty acid produced by commensal microorganisms during starch fermentation—facilitates extrathymic generation and differentiation of Foxp3+ regulatory T cells, demonstrating that metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells.
- Nicholas Arpaia
- , Clarissa Campbell
- & Alexander Y. Rudensky
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Outlook |
Vaccines: An age-old problem
Researchers are on the hunt for a better alternative to the BCG vaccine.
- Sarah DeWeerdt
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Outlook |
Latency: A sleeping giant
Most people infected with Mycobacterium tuberculosis never get the disease, but predicting who will is turning out to be a complex problem.
- Courtney Humphries
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Letter |
Stability and function of regulatory T cells is maintained by a neuropilin-1–semaphorin-4a axis
Neuropilin-1 (Nrp1) on regulatory T (Treg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of Treg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient Treg cells can maintain immune homeostasis but fail to suppress in inflammatory sites, such as tumours, providing an attractive immunotherapeutic target for the treatment of cancers.
- Greg M. Delgoffe
- , Seng-Ryong Woo
- & Dario A. A. Vignali
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Letter |
mTORC1 couples immune signals and metabolic programming to establish Treg-cell function
Here, mTORC1-dependent lipogenic programming is shown to be important for regulatory T-cell function, in part through the upregulation of the effector molecules CTLA4 and ICOS.
- Hu Zeng
- , Kai Yang
- & Hongbo Chi
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Letter |
BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis
Diverse autoimmune and allergic diseases are associated with polymorphisms in a locus encoding the transcription factor BACH2; here, BACH2 is shown to be a broad regulator of immune activation that stabilizes the differentiation of Treg cells by repressing commitment of CD4+ T cells to alternate cell fates.
- Rahul Roychoudhuri
- , Kiyoshi Hirahara
- & Nicholas P. Restifo
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Letter |
Follicular T-helper cell recruitment governed by bystander B cells and ICOS-driven motility
ICOS ligand expression by bystander B cells is shown to induce pseudopod extension and migration of CXCR5-expressing T-helper cells into B-cell follicles, where they provide help to cognate B cells for germinal centre development.
- Heping Xu
- , Xuanying Li
- & Hai Qi
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Letter |
Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress
Lymphocyte migration in the spleen is visualized live in mice using a real-time two-photon laser-scanning microscopy approach revealing that marginal zone and follicular B cells are highly motile and can shuttle between compartments, and integrin adhesion is the key to cellular retention in the marginal zone.
- Tal I. Arnon
- , Robert M. Horton
- & Jason G. Cyster
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Letter |
Ca2+ regulates T-cell receptor activation by modulating the charge property of lipids
Calcium–lipid electrostatic interactions are shown to amplify the tyrosine phosphorylation of CD3ε and CD3ζ in T-cell antigen receptor complex.
- Xiaoshan Shi
- , Yunchen Bi
- & Chenqi Xu
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Article |
Novel Foxo1-dependent transcriptional programs control Treg cell function
The results of a series of genetic experiments indicate that Foxo1 has a pivotal, Foxp3-independent role controlling regulatory T-cell function.
- Weiming Ouyang
- , Will Liao
- & Ming O. Li
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Letter |
A vaccine strategy that protects against genital herpes by establishing local memory T cells
A genital herpes simplex vaccine strategy of immunization using attenuated virus with peripheral local chemokine application can establish a population of protective tissue-resident memory T cells.
- Haina Shin
- & Akiko Iwasaki
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Letter |
Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions
IL-21- and CD40-dependent cognate interactions with T cells are identified as key drivers for the generation of IL-10-producing regulatory B cells, which can protect against autoimmune disease.
- Ayumi Yoshizaki
- , Tomomitsu Miyagaki
- & Thomas F. Tedder
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Letter |
Melanomas resist T-cell therapy through inflammation-induced reversible dedifferentiation
A genetically engineered mouse model is used to determine the mechanism of acquired resistance to adoptive therapy with cytotoxic T cells specific for a melanocytic differentiation antigen; tumour necrosis factor (TNF)-α is identified as a crucial factor that causes reversible dedifferentiation of mouse and human melanoma cells.
- Jennifer Landsberg
- , Judith Kohlmeyer
- & Thomas Tüting
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News & Views |
Tolerating pregnancy
The activity of specific suppressive immune cells, some of which persist to aid subsequent pregnancies, helps to explain how a pregnant female's immune system tolerates fetal antigens inherited from the father. See Letter p.102
- Alexander G. Betz
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Letter |
Endogenous antigen tunes the responsiveness of naive B cells but not T cells
Mature B cells encounter antigens during development that induce anergy or functional unresponsiveness; this large reservoir of dormant autoreactive B cells may serve as a pool of extended antibody specificity for purposes of protective immunity, as well as the source of pathogenic autoantibodies that characterize rheumatic diseases such as systemic lupus erythematosus.
- Julie Zikherman
- , Ramya Parameswaran
- & Arthur Weiss
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Letter |
HIV-infected T cells are migratory vehicles for viral dissemination
Using intravital microscopy, this study visualizes HIV-1-infected T cells within the lymph nodes of humanized mice, demonstrating that infected cells have reduced motility and long membrane processes; treating infected mice with a lymphocyte egress inhibitor prevents HIV-1 from spreading to the circulation during the course of treatment.
- Thomas T. Murooka
- , Maud Deruaz
- & Thorsten R. Mempel
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Research Highlights |
Human response in model mice
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Research Highlights |
How fat spurs inflammation
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Research Highlights |
Controlling natural killers
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Research Highlights |
A race to kill or be killed
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Letter |
Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting
Exome analysis of chemical-carcinogen-induced mouse tumours provides evidence for T-cell-mediated immunoselection as a mechanism of immunoediting.
- Hirokazu Matsushita
- , Matthew D. Vesely
- & Robert D. Schreiber