CD4-positive T cells articles within Nature

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• Article
  17 May 2023 | Open Access

  Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma

  Tumour-infiltrating lymphocytes from glioblastoma can recognize bacterial and gut microbial peptides.

  • Reza Naghavian
  • , Wolfgang Faigle
  •  & Roland Martin

• Matters Arising | 01 February 2023

  GOT1 constrains T_H17 cell differentiation, while promoting iT_reg cell differentiation

  • Wei Xu
  • , Chirag H. Patel
  •  & Jonathan D. Powell

• Article | 06 July 2022

  Immune tolerance of food is mediated by layers of CD4⁺ T cell dysfunction

  Immune tolerance to food is mediated by CD4⁺ T cells forming subsets of T helper cells lacking the capacity to trigger gut pathology but able to produce regulatory T cells that may suppress it.

  • Sung-Wook Hong
  • , Peter D. Krueger
  •  & Marc K. Jenkins

• Article | 04 May 2022

  Landscape of helper and regulatory antitumour CD4⁺ T cells in melanoma

  A survey of the CD4⁺ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.

  • Giacomo Oliveira
  • , Kari Stromhaug
  •  & Catherine J. Wu

• Article | 18 November 2021

  CRISPR screens unveil signal hubs for nutrient licensing of T cell immunity

  CRISPR screening and protein–protein interaction networks identify components and mechanisms of nutrient-dependent mTORC1 signalling in regulatory T cells and reveal how mTORC1 integrates immunological cues and nutrient signals for adaptive immunity.

  • Lingyun Long
  • , Jun Wei
  •  & Hongbo Chi

• Article | 27 October 2021

  Early-life inflammation primes a T helper 2 cell–fibroblast niche in skin

  Time-limited skin inflammation in neonatal mice promotes a reciprocal interaction between type 2 helper T cells and fascial fibroblasts that regulates wound repair in later life.

  • Ian C. Boothby
  • , Maxime J. Kinet
  •  & Michael D. Rosenblum

• Article | 07 July 2021

  Metabolic control of T_FH cells and humoral immunity by phosphatidylethanolamine

  Enzymes in the cytidine diphosphate–ethanolamine metabolic pathway, which promotes de novo synthesis of phosphatidylethanolamine, are shown to act as post-transcriptional mediators of the differentiation of T follicular helper (T_FH) cells, by regulating the chemokine receptor CXCR5.

  • Guotong Fu
  • , Clifford S. Guy
  •  & Hongbo Chi

• Article | 24 February 2021

  Lipid signalling enforces functional specialization of T_reg cells in tumours

  Identification of a metabolic checkpoint involving lipid signalling that is specific to regulatory T cells (T_reg cells) in the tumour microenvironment raises the possibility of targeting this checkpoint for treatment of cancer.

  • Seon Ah Lim
  • , Jun Wei
  •  & Hongbo Chi

• Article | 15 February 2021

  Metabolic support of tumour-infiltrating regulatory T cells by lactic acid

  The tumour microenvironment is low in glucose and high in the alternative metabolite lactate, which regulatory T cells are shown here to use, maintaining their ability to suppress effector immune cells.

  • McLane J. Watson
  • , Paolo D. A. Vignali
  •  & Greg M. Delgoffe

• Letter | 19 June 2019

  Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function

  Genetic, pharmacological and metabolomics experiments reveal that the malate–aspartate shuttle and mitochondrial citrate export support the differentiation of mouse T helper 1 cells, whereas succinate dehydrogenase enforces their terminal effector function.

  • Will Bailis
  • , Justin A. Shyer
  •  & Richard A. Flavell

• Letter | 02 January 2019

  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

• Letter | 19 December 2018

  Metabolic heterogeneity underlies reciprocal fates of T_H17 cell stemness and plasticity

  Phenotypically, transcriptionally and metabolically diverse subsets of T_H17 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 T_H1 cells.

  • Peer W. F. Karmaus
  • , Xiang Chen
  •  & Hongbo Chi

• Letter | 25 October 2017

  Reversing SKI–SMAD4-mediated suppression is essential for T_H17 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

• Letter | 02 February 2017

  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

• Letter | 05 May 2016

  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

• Article | 25 November 2015

  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

• Letter | 15 October 2014

  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

• Letter | 19 January 2014

  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

• Letter | 04 August 2013

  Stability and function of regulatory T cells is maintained by a neuropilin-1–semaphorin-4a axis

  Neuropilin-1 (Nrp1) on regulatory T (T_reg) cells is shown to interact with semaphorin-4a (Sema4a) to promote a program of T_reg-cell stability and survival, in part through PTEN-mediated modulation of Akt signalling; Nrp1-deficient T_reg 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

• Letter | 30 June 2013

  mTORC1 couples immune signals and metabolic programming to establish T_reg-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

• Letter | 02 June 2013

  BACH2 represses effector programs to stabilize T_reg-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 T_reg cells by repressing commitment of CD4⁺ T cells to alternate cell fates.

  • Rahul Roychoudhuri
  • , Kiyoshi Hirahara
  •  & Nicholas P. Restifo

• Letter | 24 April 2013

  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

• Article | 07 November 2012

  Novel Foxo1-dependent transcriptional programs control T_reg 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

• Research Highlights | 07 March 2012

  A race to kill or be killed

• Letter | 27 November 2011

  Response to self antigen imprints regulatory memory in tissues

  Thymus-derived regulatory T cells are activated by recognition of peripheral self antigen, persist in the target tissue on cessation of antigen exposure, and respond to re-exposure to self antigen with enhanced functional activity.

  • Michael D. Rosenblum
  • , Iris K. Gratz
  •  & Abul K. Abbas

• News | 21 September 2011

  How microbes train our immune system

  Gut bacteria coax T cells to see them as friends.

  • Alla Katsnelson

• Letter | 17 July 2011

  Control of T_H17 cells occurs in the small intestine

  • Enric Esplugues
  • , Samuel Huber
  •  & Richard A. Flavell

• Letter | 19 June 2011

  Intravenous gammaglobulin suppresses inflammation through a novel T_H2 pathway

  • Robert M. Anthony
  • , Toshihiko Kobayashi
  •  & Jeffrey V. Ravetch

• Letter | 08 June 2011

  In vivo imaging of T_reg cells providing immune privilege to the haematopoietic stem-cell niche

  • Joji Fujisaki
  • , Juwell Wu
  •  & Charles P. Lin

• News & Views | 27 April 2011

  A helping hand against autoimmunity

  The T_H17 helper cells of the immune system have a dark side: they mediate autoimmune disorders. Two drugs that prevent the differentiation and activity of these cells might be of therapeutic value. See Letters p.486 & p.491

  • Anton M. Jetten

• Letter | 17 April 2011

  Suppression of T_H17 differentiation and autoimmunity by a synthetic ROR ligand

  • Laura A. Solt
  • , Naresh Kumar
  •  & Thomas P. Burris

• Letter | 27 March 2011

  Digoxin and its derivatives suppress T_H17 cell differentiation by antagonizing RORγt activity

  • Jun R. Huh
  • , Monica W. L. Leung
  •  & Dan R. Littman

• Letter | 20 October 2010

  Generation of pathogenic T_H17 cells in the absence of TGF-β signalling

  CD4⁺ T cells that selectively produce interleukin (IL)-17 (T_H17 cells) are essential for host defence and autoimmunity. It has been thought that IL-6 and transforming growth factor (TGF)-β1 are the factors responsible for initiating the specification of T_H17 cells. Here, however, it is shown that T_H17 differentiation can occur in the absence of TGF-β signalling. IL-6, IL-23 and IL-1β effectively induced IL-17 production in naive precursors. These data reveal an alternative mode for T_H17 differentiation and the importance of IL-23.

  • Kamran Ghoreschi
  • , Arian Laurence
  •  & John J. O’Shea

• Letter | 01 April 2010

  IL25 elicits a multipotent progenitor cell population that promotes T_H2 cytokine responses

  Several non-haematopoietic-cell-derived cytokines, including interleukin (IL)25, have been implicated in inducing T helper 2 (T_H2) cell-dependent inflammation, but their precise role has been unclear. Here, IL25 is shown to promote the accumulation of multipotent progenitor cells in gut-associated lymphoid tissue. These cells can give rise to macrophage or granulocyte lineages that promote the differentiation of T_H2 cells and contribute to protective immunity against helminth infections.

  • Steven A. Saenz
  • , Mark C. Siracusa
  •  & David Artis

• Letter | 01 April 2010

  IκBζ regulates T_H17 development by cooperating with ROR nuclear receptors

  Interleukin-17-producing helper T (T_H17) cells are a distinct T-cell subset characterized by its role in autoimmune disease. Here it is shown that the development of T_H17 cells requires the transcription factor IκBζ, as well as nuclear receptors of the ROR family. Mice lacking IκBζ have a defect in T_H17 development and are resistant to the induction of experimental autoimmune encephalomyelitis. The study points to some new potential molecular targets for drugs to treat autoimmune disease.

  • Kazuo Okamoto
  • , Yoshiko Iwai
  •  & Hiroshi Takayanagi

• News & Views | 27 January 2010

  The expanding T_H2 universe

  T_H2 growth factors, which are involved in allergy and in defence against parasites, are produced by many different cell types, including a newly identified population found in fat-associated lymph clusters in the abdomen.

  • Warren Strober

• Letter | 13 January 2010

  Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate

  Immune homeostasis relies on tight control over the size of a population of regulatory T cells (T_reg) that can suppress over-exuberant immune responses. Cells commit to the T_reg lineage by upregulating the transcription factor Foxp3. Conserved non-coding DNA sequence elements at the Foxp3 locus are now shown to control the composition, size and maintenance of the T_reg cell population.

  • Ye Zheng
  • , Steven Josefowicz
  •  & Alexander Y. Rudensky