Cell death and immune response

  • Article
    | Open Access

    There are dynamic interactions between immune cells and β cells that lead to β cell destruction in the context of autoimmune diabetes. Here the authors show that TET2, a methylcytosine dioxygenase, can regulate this interaction and deletion of TET2 can prevent the autoimmune destruction of β cells in mice.

    • Jinxiu Rui
    • , Songyan Deng
    •  & Kevan C. Herold
  • Article
    | Open Access

    Mito-SEPs are small peptides that can modulate oxidative metabolism in mitochondria. Here the authors show that C15ORF48 encodes a mito-SEP, MOCCI, capable of altering mitochondria respiration to suppress inflammation, while C15ORF48 3’ untranslated region also contains a miRNA, miR-147b, that synergizes with MOCCI to modulate host anti-viral responses.

    • Cheryl Q. E. Lee
    • , Baptiste Kerouanton
    •  & Lena Ho
  • Article
    | Open Access

    Lupus pathogenesis is associated with high type 1 interferon stimulated gene (ISG) expression. Here, the authors correlate ISG expression in CD8+ T cells from lupus nephritis patients with abnormal mitochondrial function, implicating increased NAD consumption and reduced cell viability in the pathogenesis.

    • Norzawani Buang
    • , Lunnathaya Tapeng
    •  & Marina Botto
  • Article
    | Open Access

    Targeting regulatory T cells (Treg) represents a therapeutic option to abrogate tumor-associated immune suppression. Here the authors show that pharmacological degradation of BCL-XL preferentially induces apoptosis of tumor-infiltrating Treg, promoting CD8 T cell activation and anti-tumor immune responses in preclinical cancer models.

    • Ryan Kolb
    • , Umasankar De
    •  & Weizhou Zhang
  • Article
    | Open Access

    Most chemotherapeutic agents, including gemcitabine, do not elicit immunogenic cell death, a phenomenon associated with the release of damage-associated molecule patterns (DAMPs). Here, the authors show that gemcitabine-treated dying cancer cells express hallmark DAMPs but their immunogenic properties are hindered by the concomitant release of the inhibitory DAMP PGE2.

    • K. Hayashi
    • , F. Nikolos
    •  & K. S. Chan
  • Article
    | Open Access

    Anti-Ly6G or ant-Gr1 antibodies are commonly used to deplete neutrophils in vivo. Here the authors provide mechanistic insight into why these approaches may not specifically or durably reduce the number of neutrophils in mice, and also present a new method that overcomes these limitations to have potentially wide applicability in experimental studies.

    • Gael Boivin
    • , Julien Faget
    •  & Etienne Meylan
  • Article
    | Open Access

    An increasing number of inflammatory pathologies is associated with IL-1 production downstream of caspases 1 and 11. Here the authors show that graft-versus-host-disease (GvHD) is diminished in mice with genetic or pharmacological ablation of caspase-11, and provide mechanistic insights into the signals leading to caspase-11 activation in GvHD.

    • Yanyan Lu
    • , Ran Meng
    •  & Ben Lu
  • Article
    | Open Access

    Many forms of autoimmune disorder involve abnormal T cell functions, but how this versatility is achieved is not fully clear. Here the authors show that Sharpin-deficient Treg cells induce the death of local keratinocytes via multiple programmed cell death and innate inflammation to cause skin inflammation similar to cpdm mice with genetic deletion of Sharpin.

    • Katsuhiro Sasaki
    • , Ai Himeno
    •  & Kazuhiro Iwai
  • Article
    | Open Access

    Detailed characterization of cardiac damage following ischemia/reperfusion injury and detection of occurring inflammatory responses is important for the development of new therapeutic concepts. Here the authors present a method for the three-dimensional investigation of acute and chronic cardiac injury responses using light sheet fluorescence microscopy.

    • Simon F. Merz
    • , Sebastian Korste
    •  & Matthias Totzeck
  • Review Article
    | Open Access

    Immune cells adapt distinct metabolic strategies to accommodate specific functions associated with cell types or differentiation stages. Here in this review the authors discuss the nutrients, sensors, and mediators of such a metabolic adaption in nutrient-limiting immune microenvironments such as tumors or infections.

    • Nidhi Kedia-Mehta
    •  & David K. Finlay
  • Article
    | Open Access

    Certain chemotherapeutic agents can exert their anticancer effect through indirect immune-dependent mechanism. Here, the authors screen a library of tyrosine kinase inhibitors and show that crizotinib is an effective stimulator of immunogenic cell death and can potentiate the efficacy of immune checkpoint blockade.

    • Peng Liu
    • , Liwei Zhao
    •  & Guido Kroemer
  • Article
    | Open Access

    Programmed cell death regulates early development but how various factors (for example, TRADD, FADD and RIPKs) regulate this is unclear. Here, the authors show that a single allele of Tradd is essential for survival, when both Ripk3 and Ripk1 are knocked out in mice, and RIPK1 protects thymocytes from TNF-induced apoptosis.

    • John P. Dowling
    • , Mohamed Alsabbagh
    •  & Jianke Zhang
  • Article
    | Open Access

    Necroptotic cells activate MLKL and release inflammatory DAMPs, although the underlying regulatory mechanisms of this process are poorly understood. Here, Murai et al. develop a necroptosis-specific FRET sensor (SMART) that monitors MLKL membrane translocation to identify two modes of DAMP release.

    • Shin Murai
    • , Yoshifumi Yamaguchi
    •  & Hiroyasu Nakano
  • Article
    | Open Access

    Phagocytic cells of the innate immune system play critical roles in defence against invading pathogens including the opportunistic pathogen Candida albicans. Here the authors show that C. albicans derived Candidalysin in addition to being a cell-damaging toxin to mononuclear phagocytes is a trigger of NLRP3 inflammasome activation in these cells.

    • Lydia Kasper
    • , Annika König
    •  & Bernhard Hube
  • Article
    | Open Access

    Invariant Natural Killer T cells (iNKT) rapidly exert effector functions upon activation, but the mechanisms of their functional maturation remain to be determined. Here, Xu and colleagues show that the mediator subunit Med23 is a transcriptional regulator controlling iNKT cell terminal maturation.

    • Yu Xu
    • , Yang Sun
    •  & Xiaolong Liu
  • Article
    | Open Access

    Interleukin-33 (IL-33) can be released as a cytokine or transported into the nucleus, but the significance of this nuclear shuttling is not fully understood. Here the authors show that chromatin-binding of IL-33 alters, unexpectedly, the activity of IL-33 both in alarmin release kinetics and receptor signaling capacity.

    • Jared Travers
    • , Mark Rochman
    •  & Marc E. Rothenberg
  • Article
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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
    | Open Access

    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