Immunology

The Transcription Factor Runx3 Establishes Chromatin Accessibility of cis-Regulatory Landscapes that Drive Memory Cytotoxic T Lymphocyte Formation

Immunity - 17 April 2018 - 12:00am
Chromatin accessibility in naive CD8+ T cells is globally reprogrammed during infection. Wang et al. show that the transcription factor Runx3 programs chromatin accessibility during stimulation of naive CD8+ T cells, which establishes early transcriptional circuits that drive differentiation of nascent cytotoxic T lymphocytes (CTLs), and also represses terminal differentiation to ensure that they develop into long-lived memory CTLs.
Categories: Immunology

T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate

Immunity - 17 April 2018 - 12:00am
Ise et al. identify the plasma cell-prone LZ GC B cells whose generation relies on the amount of CD40 signal. Higher expression of ICAM-1 and SLAM in those cells facilitates more stable contacts with Tfh cells, suggesting that strength of Tfh-GC B cell interaction critically regulates formation of plasma cell precursors.
Categories: Immunology

An Antibody Targeting the Fusion Machinery Neutralizes Dual-Tropic Infection and Defines a Site of Vulnerability on Epstein-Barr Virus

Immunity - 17 April 2018 - 12:00am
Epstein-Barr virus is a cancer-associated pathogen for which there is no vaccine. Snijder et al. isolate a monoclonal antibody that neutralizes infection of the major cell types infected by EBV. Structural analysis of the antibody-gH/gL glycoprotein complex reveals a key site of EBV vulnerability that may pave the way for a next-generation EBV vaccine.
Categories: Immunology

T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation

Immunity - 17 April 2018 - 12:00am
It is unclear how quiescence is enforced in naive T cells, yet activation is allowed. Tu et al. show that TGF-β signaling maintains T cell quiescence. Strong TCR stimuli reduce TβRI expression and consequently abolish TGF-β signaling in T cells. TCR-mediated TβRI downregulation acts as a “third criterion” to fully activate T cells in addition to the “two-signal” model.
Categories: Immunology

Niches for Hematopoietic Stem Cells and Their Progeny

Immunity - 17 April 2018 - 12:00am
The adult bone marrow provides essential niches for hematopoietic stem cell (HSC) maintenance and differentiation, which are not fully understood. Here we review the currently known cellular and molecular components of the niche for hematopoietic stem cells and their progeny, highlight their heterogeneity and interdependency, and discuss some open questions in the field.
Categories: Immunology

Systems Medicine in Chronic Inflammatory Diseases

Immunity - 17 April 2018 - 12:00am
Chronic inflammatory diseases represent an increasing medical burden, yet neither tools to predict the individual disease course nor causal cures are at hand. We discuss opportunities for systems medicine to derive precise, individualized disease models and outline the European consortium SYSCID as part of the roadmap to clinical practice.
Categories: Immunology

Alessandro Moretta (1953–2018)

Immunity - 17 April 2018 - 12:00am
Alessandro Moretta passed away in his home in Genova at age of 64 on February 17th, 2018 after a 7-year-long fight against metastatic lung cancer. Despite the heavy chemo- and radio-therapy, he continued to successfully pursue his research, guide his coworkers, and write papers and research projects. Anti-PD1 therapy helped to provide a significant improvement of his disease in the last 3 years. Just 2 days before his death, Alessandro’s meeting with the University of Genova Rector Delegate was fundamental to obtain sufficient funding to maintain the PhD program in immunology, a program he recently accepted to direct.
Categories: Immunology

Self-Renewal and Toll-like Receptor Signaling Sustain Exhausted Plasmacytoid Dendritic Cells during Chronic Viral Infection

Immunity - 17 April 2018 - 12:00am
The mechanisms underlying the maintenance and dysfunction of exhausted pDCs during chronic viral infection are unclear. Macal and Jo et al. find that exhausted pDCs are maintained by IFN-I and TLR7 signaling via multiple mechanisms, including inhibition of bone marrow pDC generation, sustained proliferation of exhausted pDCs, and promotion of pDC functional loss, the latter of which leads to impaired host defense to secondary infection.
Categories: Immunology

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4<sup>+</sup> T cells

Nature Immunology - 16 April 2018 - 12:00am

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4+ T cells

c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4<sup>+</sup> T cells, Published online: 16 April 2018; doi:10.1038/s41590-018-0083-5

The transcription factor c-Maf controls IL-10 production in T cells. O’Garra and colleagues use systems and in vivo functional analysis of T cell subsets to reveal distinct context-specific roles for c-Maf.
Categories: Immunology

Distinct myeloid cell subsets promote meningeal remodeling and vascular repair after mild traumatic brain injury

Nature Immunology - 16 April 2018 - 12:00am

Distinct myeloid cell subsets promote meningeal remodeling and vascular repair after mild traumatic brain injury

Distinct myeloid cell subsets promote meningeal remodeling and vascular repair after mild traumatic brain injury, Published online: 16 April 2018; doi:10.1038/s41590-018-0086-2

Meningeal vascular damage accompanies mild traumatic brain injury, which persists in a fraction of patients. McGavern and colleagues report that distinct myeloid cell subsets are temporally recruited to the wound site during tissue repair; however, re-injury at early time points impairs recovery.
Categories: Immunology

Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling

Nature Immunology - 16 April 2018 - 12:00am

Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling

Fatal demyelinating disease is induced by monocyte-derived macrophages in the absence of TGF-β signaling, Published online: 16 April 2018; doi:10.1038/s41590-018-0091-5

Harris and colleagues show that the cytokine TGF-β is required for colonization of the microglial niche and maintenance of central nervous system integrity. Acute loss of TGF-β leads to proinflammatory responses and fatal demyelinating disease.
Categories: Immunology

Monomeric TCRs drive T cell antigen recognition

Nature Immunology - 16 April 2018 - 12:00am

Monomeric TCRs drive T cell antigen recognition

Monomeric TCRs drive T cell antigen recognition, Published online: 16 April 2018; doi:10.1038/s41590-018-0092-4

Higher-order TCRs have been postulated to maintain high antigen sensitivity and trigger signaling. Huppa and colleagues use various investigative techniques and find exclusively monomeric TCR–CD3 complexes that drive the recognition of antigenic pMHC.
Categories: Immunology

Bruno Kyewski 1950–2018

Nature Immunology - 11 April 2018 - 12:00am

Bruno Kyewski 1950–2018

Bruno Kyewski 1950–2018, Published online: 11 April 2018; doi:10.1038/s41590-018-0095-1

Bruno Kyewski 1950–2018
Categories: Immunology

Antibiotics as Instigators of Microbial Dysbiosis: Implications for Asthma and Allergy

Trends Immunology - 11 April 2018 - 12:00am
The human body and its resident microbiota form a complex ecosystem, shaped by both inherited and environmental factors. The use of antibiotics represents an extreme example of environmental pressure and can broadly disrupt the microbial landscape. The benefits that antibiotics have brought to modern medicine are unquestionable; however, their overuse comes with consequences, including the potential for secondary infections by opportunistic pathogens and the spread of antibiotic resistance. Here, we discuss the implications of microbial dysbiosis driven by antibiotics, with a focus on potential links with allergy and asthma.
Categories: Immunology

An Interleukin-25-Mediated Autoregulatory Circuit in Keratinocytes Plays a Pivotal Role in Psoriatic Skin Inflammation

Immunity - 10 April 2018 - 12:00am
The inflammatory mechanism of psoriasis remains incompletely understood. In this issue, Xu et al. identified IL-25 as a key pathogenic factor regulating the proliferation of keratinocytes and psoriasis development in an autocrine expression manner.
Categories: Immunology

Manganese Increases the Sensitivity of the cGAS-STING Pathway for Double-Stranded DNA and Is Required for the Host Defense against DNA Viruses

Immunity - 10 April 2018 - 12:00am
The cGAS-STING pathway is required for host defense against DNA viruses. Wang et al. find that upon virus infection, Manganese (Mn2+) is released from organelles into the cytosol and facilitates the activation of cGAS and STING. Their findings identify a role for Mn in innate immune activation and host anti-viral defense.
Categories: Immunology

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Nature Immunology - 9 April 2018 - 12:00am

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells, Published online: 09 April 2018; doi:10.1038/s41590-018-0082-6

NK cells constrain infection by cytomegalovirus. Romagnani and colleagues show that human NKG2C+ NK cells recognize distinct HCMV UL40 viral peptides, which can vary among viral isolates. NKG2C+ NK cells thereby demonstrate adaptive-like recognition that can discriminate between closely related viral strains.
Categories: Immunology

The Immune Landscape of Cancer

Immunity - 5 April 2018 - 12:00am
Thorsson et al. present immunogenomics analyses of more than 10,000 tumors, identifying six immune subtypes that encompass multiple cancer types and are hypothesized to define immune response patterns impacting prognosis. This work provides a resource for understanding tumor-immune interactions, with implications for identifying ways to advance research on immunotherapy.
Categories: Immunology

A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion

Immunity - 3 April 2018 - 12:00am
Disrupting the balance between self-renewal and differentiation of HSCs leads to severe pathologic consequences. Xia et al. identify a circular RNA cia-cGAS that is highly expressed in the nucleus of LT-HSCs. Under homeostatic conditions, cia-cGAS binds DNA sensor cGAS to block its synthase activity, protecting dormant LT-HSCs from cGAS-mediated exhaustion.
Categories: Immunology

Toll-like Receptor 9 Contains Two DNA Binding Sites that Function Cooperatively to Promote Receptor Dimerization and Activation

Immunity - 3 April 2018 - 12:00am
TLR9 recognizes DNAs with unmethylated CpG motifs and activates innate immune responses. Ohto et al. identify another TLR9 binding motif, the 5′-xCx DNA motif, and determine the tertiary structure of TLR9 in complex with CpG and 5′-xCx DNAs to reveal a cooperative activation mechanism of TLR9 by two types of DNAs.
Categories: Immunology

Pages