Cell death and immune response articles within Nature Communications

Featured

• Article
  10 May 2018 | Open Access

  The thioredoxin-1 system is essential for fueling DNA synthesis during T-cell metabolic reprogramming and proliferation

  Thioredoxin (Trx), Trx reductase, Txnip and NADPH together comprise the Trx system. Here the authors make a T cell-specific thioredoxin reductase-1 knockout mouse to show how this system reprograms cellular metabolism to enable T cell development, proliferation and responses.

  • Jonathan Muri
  • , Sebastian Heer
  •  & Manfred Kopf

• Article
  23 March 2018 | Open Access

  Transcriptomic signatures of NK cells suggest impaired responsiveness in HIV-1 infection and increased activity post-vaccination

  Natural killer (NK) cells are important for eliminating cells under stress or infected by virus, and may have a function in anti-HIV immunity. Here the authors show that different NK-activating stimuli induce distinct transcriptional fingerprints in human NK cells that are analogous to changes caused by HIV vaccination or chronic infection.

  • Margaret C. Costanzo
  • , Dohoon Kim
  •  & Michael A. Eller

• Article
  12 February 2018 | Open Access

  The p55TNFR-IKK2-Ripk3 axis orchestrates arthritis by regulating death and inflammatory pathways in synovial fibroblasts

  TNF is a major therapeutic target for rheumatoid arthritis (RA) and synovial fibroblasts are central to the pathogenesis of RA. Here the authors dissect TNF-induced death and activation signalling in RA synovial fibroblasts and TNF-driven arthritis and indicate that a successful therapeutic strategy might be to target both IKK2 and RIPK3 at the same time.

  • Marietta Armaka
  • , Caroline Ospelt
  •  & George Kollias

• Article
  27 November 2017 | Open Access

  Nano-enabled pancreas cancer immunotherapy using immunogenic cell death and reversing immunosuppression

  Pancreatic cancer remains difficult to treat mainly due to the drug delivery challenges posed by a strong stromal component. Here the authors develop nanocarriers that improve drug delivery efficiency and engage the host immune system against the tumor resulting in reduction of tumor growth and metastasis.

  • Jianqin Lu
  • , Xiangsheng Liu
  •  & Andre E. Nel

• Article
  24 October 2017 | Open Access

  Single-cell mass cytometry and transcriptome profiling reveal the impact of graphene on human immune cells

  Understanding the interaction of nanomaterials and immune cells at the biomolecular level is of great significance in therapeutic applications. Here, the authors investigated the interaction of graphene oxide nanomaterials and several immune cell subpopulations using single-cell mass cytometry and genome-wide transcriptome analysis.

  • Marco Orecchioni
  • , Davide Bedognetti
  •  & Lucia G Delogu

• Article
  05 September 2017 | Open Access

  Signalling strength determines proapoptotic functions of STING

  The cGAS/STING signalling pathway is responsible for sensing intracellular DNA and activating downstream inflammatory genes. Here the authors show mouse primary T cells and T leukaemia are hyperresponsive to STING agonist, and this strong STING signalling is associated with apoptosis induction.

  • Muhammet F. Gulen
  • , Ute Koch
  •  & Andrea Ablasser

• Article
  09 August 2017 | Open Access

  Activated NK cells cause placental dysfunction and miscarriages in fetal alloimmune thrombocytopenia

  Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a gestational disease caused by maternal immune responses against fetal platelets. Using a FNAIT mouse model and human trophoblast cell lines, here the authors show that uterine natural killer cell-mediated trophoblast apoptosis contributes to FNAIT pathogenesis.

  • Issaka Yougbaré
  • , Wei-She Tai
  •  & Heyu Ni

• Article
  07 June 2017 | Open Access

  Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

  Dysfunction of autophagy in plaque macrophages aggravates atherosclerosis. Here the authors show that induction of macrophage autophagy–lysosomal biogenesis either genetically by overexpression of the master transcriptional regulator of this process, TFEB, or pharmacologically with trehalose is atheroprotective.

  • Ismail Sergin
  • , Trent D. Evans
  •  & Babak Razani

• Article
  31 May 2017 | Open Access

  Expression of CD226 is associated to but not required for NK cell education

  CD226 is an activating receptor expressed in a co-varied manner with inhibitory receptors on natural killer (NK) cells, but whether CD226 is involved in NK cell education is unclear. Here the authors show that CD226 expression is plastic depending on the MHC environment and endows educated NK cells enhanced effector functions.

  • Arnika K. Wagner
  • , Nadir Kadri
  •  & Benedict J. Chambers

• Article
  24 May 2017 | Open Access

  Antigen-specific CD8⁺ T cell feedback activates NLRP3 inflammasome in antigen-presenting cells through perforin

  Perforin is part of the cytotoxic effector mechanism of CD8+ T cells. Here the authors show that antigen-induced perforin release from CD8 T cells into antigen-presenting cells can activate NLRP3 inflammasome to constitute a positive feedback loop to promote anti-tumour immunity and allo-responses.

  • Yikun Yao
  • , Siyuan Chen
  •  & Youcun Qian

• Article
  22 May 2017 | Open Access

  Short single-stranded DNA degradation products augment the activation of Toll-like receptor 9

  DNA degradation products are frequently found in the endosome, but how they regulate the activation of Toll-like receptors is not known. Here the authors show that single-stranded DNA as short as two nucleotides can enhance the ability of longer DNA oligonucleotides to activate Toll-like receptors.

  • Jelka Pohar
  • , Duško Lainšček
  •  & Mojca Benčina

• Article
  22 May 2017 | Open Access

  Anti-platelet factor 4/polyanion antibodies mediate a new mechanism of autoimmunity

  Antibodies against the platelet factor 4 (PF4) support bacterial host defence but in some cases may lead to heparin-induced thrombocytopenia (HIT). Nguyenet al.show that in autoimmune HIT a subset of antibodies binds strongly to PF4 causing its conformational change that leads to association of non-pathogenic PF4 antibodies and thrombotic platelet activation.

  • Thi-Huong Nguyen
  • , Nikolay Medvedev
  •  & Andreas Greinacher

• Article
  23 December 2016 | Open Access

  Fas/CD95 prevents autoimmunity independently of lipid raft localization and efficient apoptosis induction

  Fas drives apoptosis and mutations in this receptor can cause autoimmunity through failure of cell death. Here, the authors uselpr/lprmice with palmitoylation-defective mutant Fas to provide evidence that Fas might limit spontaneous autoimmunity through a non-apoptotic mechanism.

  • Anthony C. Cruz
  • , Madhu Ramaswamy
  •  & Richard M. Siegel

• Article
  15 September 2016 | Open Access

  IL-13Rα2 uses TMEM219 in chitinase 3-like-1-induced signalling and effector responses

  Chitinase 3-like 1 regulates cell death, inflammation and tissue remodelling via IL-13receptorα2. Here, the authors show that TMEM219 is a IL-13Rα2 co-receptor and modulates oxidant-induced apoptosis and lung injury, melanoma metastasis and TGF-β1 signalling, downstream of Chi3l1-IL-13Rα2.

  • Chang-Min Lee
  • , Chuan Hua He
  •  & Jack A. Elias

• Article
  22 July 2016 | Open Access

  A major secretory defect of tumour-infiltrating T lymphocytes due to galectin impairing LFA-1-mediated synapse completion

  Galectin-3 is a sugar-binding protein that can inhibit antitumour cytotoxic immunity. Here the authors show that Galectin-3 expressed by tumour cells inhibits LFA-1 on cytotoxic lymphocytes, impairing immunological synapse formation, IFNg secretion, and target cell killing.

  • Anne-Elisabeth Petit
  • , Nathalie Demotte
  •  & Pierre van der Bruggen

• Article
  07 June 2016 | Open Access

  Th2 and eosinophil responses suppress inflammatory arthritis

  Type 2 immune responses are viewed as opposites of Type 1 and 17 responses. Here the authors show that activation of Type 2 immunity by helminth infection counteracts the development of inflammatory arthritis, a type 17-mediated pathology, via IL-4/IL-13- STAT6 signalling and eosinophil activation.

  • Zhu Chen
  • , Darja Andreev
  •  & Aline Bozec

• Article
  25 May 2016 | Open Access

  Stepwise phosphorylation of p65 promotes NF-κB activation and NK cell responses during target cell recognition

  NK cell activation requires multiple signals. Here the authors show that while NKG2D, 2B4, or DNAM-1 receptor activation is insufficient to induce cytokine production, these signals synergize by Vav-1-mediated NF-κB multiphosphorylation, and this signaling checkpoint is defective in X-linked lymphoproliferative disease.

  • Hyung-Joon Kwon
  • , Go-Eun Choi
  •  & Hun Sik Kim

• Article
  23 May 2016 | Open Access

  Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable

  HIV evolves within infected persons to escape being destroyed by the immune system. Here, Barton et al. combine evolutionary dynamics and statistical physics to simulate this process, successfully predicting the relative rate and location of escape mutations in viral sequences for a cohort of HIV-infected persons.

  • John P. Barton
  • , Nilu Goonetilleke
  •  & Arup K. Chakraborty

• Article
  19 May 2016 | Open Access

  T-bet is a key modulator of IL-23-driven pathogenic CD4⁺ T cell responses in the intestine

  How transcription factor T-bet and Th17 cells contribute to colitis remains incompletely understood. Here the authors identify T-bet as a negative regulator of IL-23R pathway activation and show that T-bet deficient T cells drive colitogenic Th17 responses dependent on the cytokines IL-17A and IL-22.

  • Thomas Krausgruber
  • , Chris Schiering
  •  & Fiona Powrie

• Article
  19 May 2016 | Open Access

  ISG15 deficiency and increased viral resistance in humans but not mice

  ISG15 is a ubiquitin-like protein which has important immune-related functions in mice and humans. Here the authors demonstrate that, unlike in mice, human ISG15 stabilizes UPS18 and that ISG15-deficient human cells are more resistant to viral infection.

  • Scott D. Speer
  • , Zhi Li
  •  & Dusan Bogunovic

• Article
  18 May 2016 | Open Access

  Experimental priming of encephalitogenic Th1/Th17 cells requires pertussis toxin-driven IL-1β production by myeloid cells

  Pertussis toxin enhances the induction of autoreactive T cells in mouse models of autoimmunity. Here the authors show that stimulation of IL-1β production in myeloid cells by pertussis toxin is necessary to prime pathogenic Th1/Th17 cells in experimental autoimmune encephalopathy.

  • Francesca Ronchi
  • , Camilla Basso
  •  & Federica Sallusto

• Article
  16 May 2016 | Open Access

  Pseudomonas aeruginosa elastase cleaves a C-terminal peptide from human thrombin that inhibits host inflammatory responses

  Neutrophil elastase cleaves thrombin generating anti-inflammatory peptides. Here the authors show that cleavage of thrombin by Pseudomonas aeruginosaelastase generates a peptide that prevents TLR dimerization and signaling, interfering with the inflammatory response to avoid host defense.

  • Mariena J. A. van der Plas
  • , Ravi K. V. Bhongir
  •  & Artur Schmidtchen

• Article
  05 May 2016 | Open Access

  Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling

  Marginal zone B cells are mostly characterized in the context of host defense against bacterial blood-borne pathogens. Here the authors show that TLR4 signaling in these cells requires Fcα/μR (CD351) and that they are a major source of IL-6 in a mouse model of sepsis.

  • Shin-ichiro Honda
  • , Kazuki Sato
  •  & Akira Shibuya

• Article
  21 April 2016 | Open Access

  Virtual memory T cells develop and mediate bystander protective immunity in an IL-15-dependent manner

  Virtual memory T cells are CD8 T cells with memory phenotype present in unimmunized mice. Here the authors show that these cells have higher affinity for self-antigen, depend on IL-15 for proliferation and antigen-non-specific cytotoxicity in mice, and that a similar population exists in humans.

  • Jason T. White
  • , Eric W. Cross
  •  & Ross M. Kedl

• Article
  19 April 2016 | Open Access

  NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction

  The saw-scaled viper venom causes continued tissue damage that may cause death. Here the authors show that the venom attracts neutrophils to the bite site and induces neutrophil extracellular traps that capture venom components causing tissue damage, which can be prevented by enzymatic DNA degradation.

  • Gajanan D. Katkar
  • , Mahalingam S. Sundaram
  •  & Kempaiah Kemparaju

• Article
  12 April 2016 | Open Access

  Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity

  Clec4A4 is a C-type lectin receptor highly expressed by CD8α⁻ dendritic cells. Here the authors show that its loss of function results in enhanced T cell responses and exacerbated autoimmunity, implicating Clec4A4 in limiting activation of the CD8α⁻dendritic cells.

  • Tomofumi Uto
  • , Tomohiro Fukaya
  •  & Katsuaki Sato

• Article
  03 March 2016 | Open Access

  EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity

  EAF2 has been previously known as a transcriptional elongation factor and a proapoptotic gene lost in prostate cancer. Here the authors show that EAF2 is required for apoptosis of germinal centre B cells, and that EAF2-deficient mice develop excessive antibody responses and autoimmunity.

  • Yingqian Li
  • , Yoshimasa Takahashi
  •  & Ji-Yang Wang

• Article
  19 February 2016 | Open Access

  Influenza A virus targets a cGAS-independent STING pathway that controls enveloped RNA viruses

  Stimulator of interferon genes (STING) is known to be involved in defence against DNA viruses, but its role in the control of RNA viruses remains poorly explored. Here the authors show that STING participates in an innate immune response to RNA virus infection in a cGAS-independent manner.

  • Christian K. Holm
  • , Stine H. Rahbek
  •  & Søren R. Paludan

• Article
  17 February 2016 | Open Access

  Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints

  Blocking immune checkpoints is a promising strategy to treat lung cancer, but patients often become resistant to the therapy. Here, the authors analyse resistance in mouse models of lung cancer and show in mice and two patients, an increase in the expression of TIM3, which is also involved in the immune response to cancer.

  • Shohei Koyama
  • , Esra A. Akbay
  •  & Peter S. Hammerman

• Article
  29 January 2016 | Open Access

  Inactivation of nuclear GSK3β by Ser³⁸⁹ phosphorylation promotes lymphocyte fitness during DNA double-strand break response

  Double stranded DNA breaks are generated during rearrangements of lymphocyte antigen receptors. Here the authors show that the DNA breaks induce phosphorylation of nuclear GSK3β at Ser³⁸⁹/Thr³⁹⁰, protecting the activated lymphocytes from necroptosis-mediated cell death.

  • Tina M. Thornton
  • , Pilar Delgado
  •  & Mercedes Rincón

• Article
  05 January 2016 | Open Access

  DCAF1 controls T-cell function via p53-dependent and -independent mechanisms

  DCAF1 (VprBP), an HIV target protein, is a component of an ubiquitin ligase complex involved in developmental processes in plants and animals. Here, DCAF1 is shown to be vital for activation-induced T cell growth and proliferation, partly by being required for p53’s ubiquitination and degradation.

  • Zengli Guo
  • , Qing Kong
  •  & Yisong Y. Wan

• Article
  05 January 2016 | Open Access

  Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response

  During an immune response, CD4+ T cell repertoire is thought to increase in avidity at the expense of diversity. Here the authors show that B cells act as antigen-presenting cells to boost the development of low-avidity T cell clones, diversifying the T cell repertoire at late stages of the response.

  • Julia Merkenschlager
  • , Mickaël J. Ploquin
  •  & George Kassiotis

• Article
  04 January 2016 | Open Access

  Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles

  Tumour samples are heterogeneous and are comprised of multiple cell types in addition to cancer cells. Here, the authors devised a method to estimate the relative levels of haematopoietic cells in breast cancer samples and demonstrate that this correlates with prognosis.

  • Frederick S. Varn
  • , Erik H. Andrews
  •  & Chao Cheng

• Article
  27 July 2015 | Open Access

  Genetic, molecular and physiological basis of variation in Drosophila gut immunocompetence

  Animals rely on a multitude of resistance and tolerance mechanisms to resist harmful gut microbes. Here, the authors explore the genetic, molecular and physiological basis underlying the remarkable phenotypic variation in resistance to enteric bacterial infection inDrosophila melanogaster.

  • Maroun S. Bou Sleiman
  • , Dani Osman
  •  & Bart Deplancke

• Article
  27 March 2015 | Open Access

  Myeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization

  In response to microbial ligands, IRF5 promotes pro-inflammatory M1 macrophage activation and production of nitrous oxide. Here the authors show that nitrous oxide modifies IRF5 tyrosine residues as a negative feedback, limiting the inflammatory response and protecting from endotoxin shock.

  • Geming Lu
  • , Ruihua Zhang
  •  & Huabao Xiong

• Article
  01 December 2014 | Open Access

  Oligodendrocyte ablation triggers central pain independently of innate or adaptive immune responses in mice

  Whether oligodendrocytes have a role in the development of chronic pain is not clear. Here the authors show that oligodendrocyte depletion causes a neuropathic pain that sets in before demyelination and is independent of immune cell activation and infiltration.

  • Simon Gritsch
  • , Jianning Lu
  •  & Rohini Kuner

• Article | 23 May 2014

  Epidermal cells help coordinate leukocyte migration during inflammation through fatty acid-fuelled matrix metalloproteinase production

  Metabolic regulation is emerging as an important component of immune response control and may be implicated in the development of inflammatory diseases. Here, the authors show that inflammatory leukocyte recruitment depends on mitochondrial metabolism in epidermal cells in zebrafish.

  • Christopher J. Hall
  • , Rachel H. Boyle
  •  & Philip S. Crosier