Featured
-
-
Article |
The TSC-mTOR pathway regulates macrophage polarization
Distinct macrophage phenotypes are associated with their polarization to a proinflammatory or alternative state, but it is not well understood how metabolic status affects this process. Here, Byles et al.demonstrate that the mTOR metabolic pathway regulates macrophage differentiation.
- Vanessa Byles
- , Anthony J. Covarrubias
- & Tiffany Horng
-
Article |
Thymic epithelial cell expansion through matricellular protein CYR61 boosts progenitor homing and T-cell output
Thymic epithelial cells provide the microenvironment required for the expansion of T cells in the thymus, but their exact function is not well understood. Here, the authors report that thymic epithelial cells are the source of matricellular protein CYR61, which is involved in thymic function and T cell development.
- Yalin Emre
- , Magali Irla
- & Beat A. Imhof
-
Article |
Integrin CD11b negatively regulates BCR signalling to maintain autoreactive B cell tolerance
Polymorphisms in the integrin gene CD11bare associated with susceptibility to systemic lupus erythematosus, but how this relates to the function of this integrin has not been fully investigated. Here, the authors report that CD11b has a role in the intrinsic maintenance of autoreactive B cell tolerance by regulating BCR signalling.
- Chuanlin Ding
- , Yunfeng Ma
- & Jun Yan
-
Article |
Downsizing a human inflammatory protein to a small molecule with equal potency and functionality
Replicating the functionality of bioactive proteins using rationally designed small molecule mimics is both economically valuable and synthetically challenging. Here the authors develop a mimic of the inflammatory protein C3a with equal biological potency but enhanced stability and bioavailability.
- Robert C. Reid
- , Mei-Kwan Yau
- & David P. Fairlie
-
Article |
VapC20 of Mycobacterium tuberculosis cleaves the Sarcin–Ricin loop of 23S rRNA
Toxin–antitoxin systems have been implicated in the pathogenicity of Mycobacterium tuberculosis. Here, the authors study the function of the M. tuberculosistoxin VapC20 and show that it can impair protein translation and inhibit bacterial growth by cleaving the Sarcin–Ricin loop of 23S rRNA
- Kristoffer S. Winther
- , Ditlev E. Brodersen
- & Kenn Gerdes
-
Article |
Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides
Cytotoxic CD8+ T cells provide one level of protection against influenza infection. Here, the authors present evidence, in mice and humans, for the emergence and reversion of influenza A virus escape mutants associated with the immune pressure from cytotoxic CD8+ T lymphocytes.
- Sophie A. Valkenburg
- , Sergio Quiñones-Parra
- & Katherine Kedzierska
-
Article |
Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation
Allergic airway inflammation in asthma can be treated with corticosteroids, but some patients remain unresponsive to this therapy. Here, Kabata et al. show that thymic stromal lymphopoietin contributes to the corticosteroid resistance during airway inflammation through its action on natural helper cells.
- Hiroki Kabata
- , Kazuyo Moro
- & Koichiro Asano
-
Article |
Using synthetic templates to design an unbiased multiplex PCR assay
Immunosequencing enables cost-effective sequencing of repertoires of immune cells, but it often suffers from amplification biases when attempting cell quantification. Here, the authors present a powerful multiplex PCR assay that allows for quantitative and unbiased analysis of frequency of different T cell receptors.
- Christopher S. Carlson
- , Ryan O. Emerson
- & Harlan Robins
-
Article |
Perpetual expression of PAMPs necessary for optimal immune control and clearance of a persistent pathogen
Pathogen-associated molecular patterns are involved in the initiation of anti-pathogen immunity but their importance for sustaining this response is not established. Here, the authors show that persistent presence of pathogen-associated molecular patterns is required to maintain robust immune responses to pathogens.
- Samarchith P. Kurup
- & Rick L. Tarleton
-
Article |
Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signalling pathway
Sepsis in patients is often accompanied by thrombocytopenia, but the exact role of platelets in the pathogenesis of septicaemia has not been elucidated. Here, Xiang et al. present evidence that platelets may act as anti-inflammatory cells and protect from septic shock.
- Binggang Xiang
- , Guoying Zhang
- & Zhenyu Li
-
Article |
Crossreactivity of a human autoimmune TCR is dominated by a single TCR loop
Autoimmune T cell receptors can interact with both self and microbial antigens, but the structural basis for crossreactivity is not fully understood. Here, the authors provide structural insights into binding characteristics of the autoreactive T cell receptor Hy.1B11 to both self and pathogen-derived peptides.
- Dhruv K. Sethi
- , Susana Gordo
- & Kai W. Wucherpfennig
-
Article
| Open AccessInferring tumour purity and stromal and immune cell admixture from expression data
Tumour biopsies contain contaminating normal cells and these can influence the analysis of tumour samples. In this study, Yoshihara et al.develop an algorithm based on gene expression profiles from The Cancer Genome Atlas to estimate the number of contaminating normal cells in tumour samples.
- Kosuke Yoshihara
- , Maria Shahmoradgoli
- & Roel G.W. Verhaak
-
Article
| Open AccessApical membrane antigen 1 mediates apicomplexan parasite attachment but is dispensable for host cell invasion
Plasmodium and Toxoplasma apical membrane antigen 1 (AMA1) is believed to be actively involved in host cell invasion by these parasites. Bargieri et al. now demonstrate that although AMA1 facilitates adhesion, invasion can proceed in the absence of the protein.
- Daniel Y. Bargieri
- , Nicole Andenmatten
- & Robert Ménard
-
Article |
Plant immune response to pathogens differs with changing temperatures
Plants have two mechanisms to respond to infection; pattern-triggered immunity detects conserved microbial compounds, whereas effector-triggered immunity recognizes proteins secreted by pathogens. In this study, Cheng et al. report that temperature determines which of these immune systems is preferentially induced.
- Cheng Cheng
- , Xiquan Gao
- & Ping He
-
Article |
ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48
ORMDL3has been identified as a gene associated with asthma susceptibility, but its exact role in the pathogenesis of this disease is not well known. Here, the authors propose that induction of ORMDL3 in eosinophils modulates the expression of integrins, which could contribute to a key inflammatory event in asthma.
- Sung Gil Ha
- , Xiao Na Ge
- & P. Sriramarao
-
Article
| Open AccessGenome-wide mapping of gene–microbiota interactions in susceptibility to autoimmune skin blistering
The pathogenesis of inflammatory disorders afflicting the skin is multifactorial. Srinivas et al. show that diversity of the skin microbiota is a critical factor determining the susceptibility to epidermolysis bullosa acquisita, a chronic mucocutaneous autoimmune skin blistering disease.
- Girish Srinivas
- , Steffen Möller
- & Saleh M. Ibrahim
-
Article |
Inflammation-induced proteolytic processing of the SIRPα cytoplasmic ITIM in neutrophils propagates a proinflammatory state
SIRPα is an anti-inflammatory signalling receptor expressed on neutrophils. Here Zenet al.show that during inflammation, SIRPα signalling is inhibited by cleavage of its intracellular signalling motif.
- Ke Zen
- , Yalan Guo
- & Yuan Liu
-
Article
| Open AccessQuantal and graded stimulation of B lymphocytes as alternative strategies for regulating adaptive immune responses
B lymphocytes respond to stimulation by proliferating and differentiating. Here the authors quantify and model the responses of B lymphocytes to TLR and CD40-dependent stimulation, and find that the latter induces a more complex response to signals of varying strength.
- E.D. Hawkins
- , M.L. Turner
- & P.D. Hodgkin
-
Article
| Open AccessIMGT/HighV QUEST paradigm for T cell receptor IMGT clonotype diversity and next generation repertoire immunoprofiling
Dynamic changes in T cell repertoire underlie immune responses during infection, allergy, autoimmunity and cancer. Here, Li et al. present a workflow for high throughput sequencing and analysis of T cell receptor sequences, and use it to monitor the T cell response to influenza vaccination in a human patient.
- Shuo Li
- , Marie-Paule Lefranc
- & Eric J. Gowans
-
Article
| Open Accessp53 increases MHC class I expression by upregulating the endoplasmic reticulum aminopeptidase ERAP1
The protein p53 is an important tumour suppressor. Here Wanget al.show that p53 can induce expression of MHC class I on the cell surface by promoting expression of the aminopeptidase ERAP1, and that this mechanism operates in cancer cells as well as those infected with influenza virus.
- Bei Wang
- , Dandan Niu
- & Ee Chee Ren
-
Article
| Open AccessLRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition
Inflammasomes promote the maturation of inflammatory cytokines in response to signals associated with damage and infection, but it remains unclear how these signals are attenuated. Here, the authors show that the NLRP3 inflammasome is inhibited by LRRFIP2 through recruitment of the protein Flightless I.
- Jing Jin
- , Qian Yu
- & Xuetao Cao
-
Article |
NF-κB non-cell-autonomously regulates cancer stem cell populations in the basal-like breast cancer subtype
Aggressive types of breast cancer often exhibit constitutive activation of the pro-inflammatory transcription factor NF-κB. Here, Yamamoto et al. show that, in basal-like breast cancer, NF-κB upregulates the Notch receptor ligand JAG1 in non-cancer stem cells and thereby induces proliferation of breast cancer stem cells.
- Mizuki Yamamoto
- , Yuu Taguchi
- & Jun-ichiro Inoue
-
Article |
Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells
The differentiation of naive CD4 T cells into T-helper-cell subsets is thought to be influenced by factors in the T-cell environment. Martin et al.reveal that cell intrinsic differences also determine lineage commitment and show that cells with the highest avidity for self are most likely to become induced regulatory T cells.
- Bruno Martin
- , Cédric Auffray
- & Bruno Lucas
-
Article |
The RAG2 C-terminus and ATM protect genome integrity by controlling antigen receptor gene cleavage
Mice lacking the C-terminal non-core domain of RAG2 and ATM mutant mice develop thymic lymphomas harbouring recurrentTcra/d–Ightranslocations. Here the authors show that ATM and the non-core domain of RAG2 prevent bi-locus recombination by modulating higher-order chromatin structure.
- Julie Chaumeil
- , Mariann Micsinai
- & Jane A. Skok
-
Article |
Recognition of vitamin B metabolites by mucosal-associated invariant T cells
T-cell receptors expressed on mucosal-associated invariant T cells function in a similar manner to innate immune receptors by recognizing small molecules such as microbial metabolites. Here, the authors report structures of this receptor in complex with vitamin B metabolites presented by the MHC-like protein MR1.
- Onisha Patel
- , Lars Kjer-Nielsen
- & Jamie Rossjohn
-
Article |
The ARNT–STAT3 axis regulates the differentiation of intestinal intraepithelial TCRαβ+CD8αα+ cells
Intraepithelial lymphocytes (IELs) defend against pathogens in the gut, and their differentiation depends on both diet and microbiota-derived factors. Nakajima et al. show that signalling through the aryl hydrocarbon receptor nuclear translocator and STAT3 is required for the development of a subset of IELs.
- Kohei Nakajima
- , Yoichi Maekawa
- & Koji Yasutomo
-
Article
| Open AccessBacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages
Bacterial infections can influence disease outcome in influenza infection; however, the mechanisms mediating these complex interactions remain unclear. Wang et al. reveal how infection with a component of the airway microbiota enhances survival during influenza infection via induction of anti-inflammatory macrophages.
- Jian Wang
- , Fengqi Li
- & Zhigang Tian
-
Article |
Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing
Hydrogen peroxide attracts immune cells and induces wound inflammation. Evans et al. show that hydrogen peroxide also leads to the production of thymosin β4–sulfoxide in zebrafish wounds and in mouse hearts after myocardial infarction, where it acts as an anti-inflammatory factor that promotes wound healing.
- Mark A. Evans
- , Nicola Smart
- & Paul R. Riley
-
Article
| Open AccessExploring the MHC-peptide matrix of central tolerance in the human thymus
T cells learn to tolerate self-antigens in the thymus, where self-peptides are presented by thymic antigen-presenting cells. Here, the authors present an ex vivomass spectrometric analysis of the self-peptide repertoire associated with MHC I and II in human thymic tissue.
- Eleni Adamopoulou
- , Stefan Tenzer
- & Christina Stoeckle
-
Article |
B7-H5 costimulates human T cells via CD28H
The end-result of stimulation of T-cell receptors by antigen is in part determined by co-signalling pathways such as the B7/CD28 axis. Zhu et al.identify a novel costimulatory CD28-like receptor and ligand pathway in human T cells.
- Yuwen Zhu
- , Sheng Yao
- & Lieping Chen
-
Article |
An essential role for the N-terminal fragment of Toll-like receptor 9 in DNA sensing
Toll-like receptor 9 detects microbial DNA, and is activated by cleavage in the endolysosome. Onji et al. discover that following cleavage, the two parts of the protein remain associated, and this interaction is required for DNA sensing.
- Masahiro Onji
- , Atsuo Kanno
- & Kensuke Miyake
-
Article |
Persistent infection with Crohn’s disease-associated adherent-invasive Escherichia coli leads to chronic inflammation and intestinal fibrosis
Intestinal infection with adherent-invasive Escherichia coliis associated with Crohn’s disease in humans; however, its functional role remains unclear, in part due to a lack of animal models, which sustain chronic disease. Here the authors establish such a model in mice and show that it shares features with human Crohn’s disease.
- Cherrie-Lee N. Small
- , Sarah A. Reid-Yu
- & Brian K. Coombes
-
Article |
HSV-1 exploits the innate immune scavenger receptor MARCO to enhance epithelial adsorption and infection
Herpes simplex virus type 1 infects human skin and mucous membranes. MacLeod and colleagues identify MARCO as a novel cell-surface receptor bound by herpes simplex virus type 1, and show that this interaction enhances infection of keratinocytes and promotes the development of skin lesions in mice.
- Daniel T. MacLeod
- , Teruaki Nakatsuji
- & Richard L. Gallo
-
Article |
The basis for limited specificity and MHC restriction in a T cell receptor interface
Although structural insights into antigen recognition by T cell receptors are increasingly available, the thermodynamic underpinnings are less well understood. Here the authors deconstruct the energetics of a representative interface and discover that peptide specificity, cross-reactivity and MHC restriction can be inextricably linked.
- Kurt H. Piepenbrink
- , Sydney J. Blevins
- & Brian M. Baker
-
Article |
Sam68 modulates the promoter specificity of NF-κB and mediates expression of CD25 in activated T cells
The NF-κB complex is a core regulator of inflammatory gene expression and activates transcription of many different target genes. Fu et al. show that NF-κB promoter specificity can be tuned by Sam68, which is required for targeting NF-κB to the CD25 promoter during T cell activation.
- Kai Fu
- , Xin Sun
- & Fengyi Wan
-
Article |
Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation
Monocytes are recruited to sites of damage or infection where they differentiate into inflammatory macrophages. Here the authors demonstrate that, contrary to the prevailing model, these differentiated cells are able to proliferate at sites of inflammation.
- Luke C. Davies
- , Marcela Rosas
- & Philip R. Taylor
-
Article |
Crystal structures of interleukin 17A and its complex with IL-17 receptor A
Interleukin-17A homodimers preferentially interact with heterodimeric IL-17 receptors. By solving the crystal structure of an IL-17A homodimer in complex with a single IL-17RA receptor subunit, the authors reveal conformational changes in IL-17A that lead to exclusion of a second IL-17RA subunit.
- Shenping Liu
- , Xi Song
- & Matthew C. Griffor
-
Article |
High doses of CpG oligodeoxynucleotides stimulate a tolerogenic TLR9–TRIF pathway
CpG oligodeoxynucleotides stimulate innate immune signalling and are of significant interest as therapeutics. Here the authors show that at high doses, these molecules induce an opposite, tolerogenic effect, acting through a previously uncharacterized Toll-like receptor-dependent pathway.
- Claudia Volpi
- , Francesca Fallarino
- & Paolo Puccetti
-
Article |
Toll-like receptor 3 recognizes incomplete stem structures in single-stranded viral RNA
Toll-like receptor 3 is a sensor of viral infection and sterile tissue necrosis, and is known to be activated by double-stranded RNA. Tatematsu et al. demonstrate that TLR3 also recognizes incomplete stem structures that form in single-stranded poliovirus RNA.
- Megumi Tatematsu
- , Fumiko Nishikawa
- & Misako Matsumoto
-
Article
| Open AccessPrimary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci
Tumours are thought to pave the way for metastases to distant organs by secreting factors create regions of increased vascular permeability. Hiratsuka et al.identify innate immune pathways that underlie this process in the pre-metastatic lungs of tumour-bearing mice and patients.
- Sachie Hiratsuka
- , Sachie Ishibashi
- & Yoshiro Maru
-
Article
| Open AccessGANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy
The affinity of antibodies for their targets is enhanced by somatic hypermutation, in which the cytidine deaminase AID is recruited to immunoglobulin variable region genes in B cells. Here the authors show that the nuclear protein GANP has an important role in this process by modifying chromatin structure and enhancing AID recruitment.
- Shailendra Kumar Singh
- , Kazuhiko Maeda
- & Nobuo Sakaguchi
-
Article |
Regulation of asymmetric cell division and polarity by Scribble is not required for humoral immunity
B cells are thought to divide asymmetrically to generate distinct lineages required for adaptive immunity. Hawkins et al. find that surprisingly, mice lacking components of a complex required for asymmetric cell division display normal responses to vaccination and viral infection.
- Edwin D. Hawkins
- , Jane Oliaro
- & Sarah M. Russell
-
Article
| Open AccessBasophils are required for the induction of Th2 immunity to haptens and peptide antigens
Both dendritic cells and basophils have been shown to influence T helper 2 cell induction, however the relative importance of their roles remains unclear. Otsuka et al. find that basophils present hapten and peptide antigens to T cells, but are unable to present protein antigens in the absence of dendritic cells.
- Atsushi Otsuka
- , Saeko Nakajima
- & Kenji Kabashima
-
Article
| Open AccessMicrobe-dependent CD11b+ IgA+ plasma cells mediate robust early-phase intestinal IgA responses in mice
Intestinal plasma cells contribute to the delicate balance between immunity against pathogens and tolerance of intestinal microflora. Kunisawa et al. identify a subpopulation of plasma cells whose proliferation depends on stimulation by microbes and IL-10, and which mediate early-phase responses to oral antigens.
- Jun Kunisawa
- , Masashi Gohda
- & Hiroshi Kiyono
-
Article
| Open AccessMutually exclusive regulation of T cell survival by IL-7R and antigen receptor-induced signals
Before antigen exposure, T cell survival is dependent on signalling stimulated by IL-7. Koenen et al. show that upon encountering specific antigen, T cell receptor signalling initiates a different set of survival pathways, which actively suppress those that sustain naive T cells.
- Paul Koenen
- , Susanne Heinzel
- & Philip D. Hodgkin
-
Article
| Open AccessProstaglandin E2 promotes Th1 differentiation via synergistic amplification of IL-12 signalling by cAMP and PI3-kinase
Activation of cAMP signalling by prostaglandin E2 (PGE2) has long been thought to suppress Tcell receptor activation and Th1 cell differentiation. Yao et al. reveal that dual stimulation of both cAMP and PI 3-kinase pathways by PGE2 synergistically promotes Th1 differentiation by amplifying IL-12 and IFN-γsignalling.
- Chengcan Yao
- , Takako Hirata
- & Shuh Narumiya
-
Article
| Open AccessInhibition of PDE4B suppresses inflammation by increasing expression of the deubiquitinase CYLD
Phosphodiesterase 4 inhibitors are under development as anti-inflammatory drugs, however, their mechanisms of action remain poorly understood. Komatsu et al. show that Rolipram, a specific inhibitor of PDE4, reduces inflammation in a model of middle ear infection by upregulating the deubiquitinase CYLD.
- Kensei Komatsu
- , Ji-Yun Lee
- & Jian-Dong Li
-
Article |
FBXW7α attenuates inflammatory signalling by downregulating C/EBPδ and its target gene Tlr4
The innate immune sensor Toll-like receptor 4 controls inflammatory gene expression. Here the authors identify a network of positive and negative feedback loops involving the transcription factor C/EBPd and ubiquitin ligase substrate adaptor FBXW7a that regulate TLR4 levels and inflammatory signalling.
- Kuppusamy Balamurugan
- , Shikha Sharan
- & Esta Sterneck
-
Article |
Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking
Klf5 is a transcription factor that regulates self-renewal of pluripotent stem cells. Here the authors test the function of Klf5 in somatic stem cells, and discover that it controls stem cell homing and adhesion by regulating endocytosis of beta integrins.
- E. Taniguchi Ishikawa
- , K. H. Chang
- & J. A. Cancelas
Browse broader subjects
Browse narrower subjects
- Adaptive immunity
- Antigen processing and presentation
- Antimicrobial responses
- Applied immunology
- Autoimmunity
- Bone marrow transplantation
- Cell death and immune response
- Chemokines
- Coagulation system
- Complement cascade
- Cytokines
- Gene regulation in immune cells
- Haematopoiesis
- Imaging the immune system
- Immune cell death
- Immune evasion
- Immunogenetics
- Immunological disorders
- Immunotherapy
- Infection
- Infectious diseases
- Inflammation
- Innate immune cells
- Innate immunity
- Lymphatic system
- Lymphocytes
- Lymphoid tissues
- Mucosal immunology
- Neuroimmunology
- Osteoimmunology
- Plant immunology
- Signal transduction
- Translational immunology
- Transplant immunology
- Tumour immunology
- Vaccines