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A Hen in the Wolf Den: A Pathobiont Tale

17 April 2018 - 12:00am
Disruption of the gut microbiota is thought to contribute to disease onset in individuals with a genetic predisposition to autoimmunity. In a recent issue of Science, Manfredo Vieira et al. (2018) identify translocation of the gut commensal Enterococcus gallinarum into the liver as a trigger for the autoimmune disease systemic lupus erythematous.
Categories: Immunology

NLRP6 and Dysbiosis: Avoiding the Luring Attraction of Over-Simplification

17 April 2018 - 12:00am
Identification of the individual factors contributing to the formation of “healthy” or disease-modulating “dysbiotic” microbiome communities is an important aspect of microbiome research. In light of the high individuality of human and animal microbiomes across geography and time, the reproducibility of findings between different labs is increasingly recognized as a challenge to this exponentially expanding field.
Categories: Immunology

Defining the Impact of Host Genotypes on Microbiota Composition Requires Meticulous Control of Experimental Variables

17 April 2018 - 12:00am
Commensal microbial communities play critical roles in shaping human health. A substantial body of scientific and clinical evidence links microbial dysbiosis to inflammatory bowel diseases, metabolic disease, and numerous other diseases that affect humanity. One of the challenges ahead in realizing the full biomedical potential of microbiome modulation lies in defining the host and environmental factors and mechanisms that modulate the microbiota composition. There is no doubt that microbiota regulation is complex and multi-factorial, with effects from diverse cues including lifestyle, infections, diet, metabolism, and host genetics.
Categories: Immunology

TGF-β Inhibition and Immunotherapy: Checkmate

17 April 2018 - 12:00am
Immune checkpoint therapy can induce durable remissions, but many tumors demonstrate resistance. In a recent issue of Nature, Mariathasan et al. (2018) and Tauriello et al. (2018) identify stromal TGF-β signaling as a determinant of immune exclusion. Combination TGF-β inhibition and immunotherapy induces complete responses in mouse models.
Categories: Immunology

Inhibiting EBV: The Key to Carefree Smooching

17 April 2018 - 12:00am
There are no vaccines or therapies to treat Epstein-Barr virus (EBV). Snijder et al. (2018) isolated a potent human antibody against EBV that blocks infection of both B cells and epithelial cells. Structural analysis of the antibody complexed with a viral surface protein complex identified a site that may be useful in vaccine development.
Categories: Immunology

Peroxisome-Mediated Metabolism Is Required for Immune Response to Microbial Infection

17 April 2018 - 12:00am
(Immunity 47, 93-106, July 18, 2017)
Categories: Immunology

Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis

17 April 2018 - 12:00am
(Immunity 47, 875–889, November 21, 2017)
Categories: Immunology

Bach2: An Instrument of Heterogeneity for Long-Term Protection

17 April 2018 - 12:00am
Generation of functionally diverse effector and memory killer T cells is essential for immediate and long-term protective immunity. Herndler-Brandstetter et al. (2018) report that Bach2 promotes functional plasticity of effector T cells and the transition into the long-term memory compartment by regulating the expression of the inhibitory receptor KLRG1.
Categories: Immunology

GoldiRunx and Remembering Cytotoxic Memory

17 April 2018 - 12:00am
The molecular basis for T cell memory differentiation remains elusive. Wang et al. (2018) identify Runx3 as an initiating transcription factor that specifies regulatory regions required for cytotoxic T cell (CTL) memory differentiation early after TCR signaling and constrains the ability of T-bet to drive terminal effector generation.
Categories: Immunology

Innate Immune Cells Speak Manganese

17 April 2018 - 12:00am
Some metal ions, such as Ca2+ and Zn2+, are involved in intracellular communication in immune cells by acting as second messengers. In this issue of Immunity, Wang et al. (2018) present findings implying a similar role for an additional metal ion, by showing that manganese participates in the recognition of cytoplasmic DNA.
Categories: Immunology

Better Together: B7S1 Checkpoint Blockade Synergizes with anti-PD1

17 April 2018 - 12:00am
T cell checkpoint blockades can produce durable clinical responses, but only some patients and cancer types respond. In this issue of Immunity, Li et al. (2018) show B7S1-B7S1R signaling additionally regulates CD8+ T cell responses by working with the PD1-PDL1 checkpoint to block anti-tumor immunity.
Categories: Immunology

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

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

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

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

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

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

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)

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

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

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

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

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