Immune Regulation News Volume 11.27 | Jul 26 2019

TOP STORY

T Cell-Mediated Regulation of the Microbiota Protects against Obesity

Expansion of Desulfovibrio and loss of Clostridia were key features associated with obesity in a model and were present in humans with metabolic syndrome. T cell-dependent events were required to prevent disease, and replacement of Clostridia rescued obesity. [Science] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Cutaneous TRPV1⁺ Neurons Trigger Protective Innate Type 17 Anticipatory Immunity

Researchers used TRPV1-Ai32 optogenetic mice and cutaneous light stimulation to activate cutaneous neurons in the absence of tissue damage or pathogen-associated products. They found that TRPV1⁺ neuron activation was sufficient to elicit a local type 17 immune response that augmented host defense to C. albicans and S. aureus. [Cell] Abstract | Press Release | Graphical Abstract

CAR-T Cells Secreting BiTEs Circumvent Antigen Escape without Detectable Toxicity

Scientists developed a bicistronic construct to drive expression of a chimeric antigen receptor (CAR) specific for EGFRvIII, a glioblastoma-specific tumor antigen, and a bispecific T-cell engager (BiTE) against EGFR, an antigen frequently overexpressed in glioblastoma but also expressed in normal tissues. [Nat Biotechnol] Abstract | Press Release

The Mechanism of Anti-PD-L1 Antibody Efficacy against PD-L1 Negative Tumors Identifies NK Cells Expressing PD-L1 as a Cytolytic Effector

Investigators showed that some tumors can induce PD-L1 on NK cells via AKT signaling, resulting in enhanced NK cell function and preventing cell exhaustion. [Cancer Discov] Abstract | Press Release

Temporally Distinct Functions of the Cytokines IL-12 and IL-23 Drive Chronic Colon Inflammation in Response to Intestinal Barrier Impairment

The authors showed that altered Schaedler flora, a benign minimal microbiota, was sufficient to trigger colitis in a mouse model of intestinal barrier impairment. Colitis development required myeloid-cell-specific adaptor protein MyD88 signaling and was orchestrated by the cytokines IL-12, IL-23, and IFN-γ. [Immunity] Abstract | Graphical Abstract

Treg Cells Promote the SREBP1-Dependent Metabolic Fitness of Tumor-Promoting Macrophages via Repression of CD8⁺ T Cell-Derived Interferon-γ

Scientists showed that Treg cells shaped the transcriptional landscape across multiple tumor-infiltrating immune cell types. Treg cells suppressed CD8⁺ T cell secretion of interferon-γ, which would otherwise block the activation of sterol regulatory element-binding protein 1 (SREBP1)-mediated fatty acid synthesis in immunosuppressive tumor-associated macrophages. [Immunity] Abstract | Graphical Abstract

Regulation of Antitumor CD8 T-Cell Immunity and Checkpoint Blockade Immunotherapy by Neuropilin-1

Researchers showed that neuropilin-1 defines a subset of CD8⁺ T cells displaying PD-1^hi status and infiltrating human lung cancer. [Nat Commun] Full Article

CD160 Serves as a Negative Regulator of NKT Cells in Acute Hepatic Injury

By analyzing CD160^−/− mice and mixed bone marrow chimeras, the authors showed that CD160 was not essential for natural killer T (NKT) cell development. [Nat Commun] Full Article

SLAMF9 Regulates pDC Homeostasis and Function in Health and Disease

By generating CRISPR/Cas9 SLAMF9 knockout mice, researchers analyzed the role of this receptor in plasmacytoid dendritic cells, which preferentially expressed the SLAMF9 transcript and protein. These cells displayed a unique capacity to produce type I IFN and bridged between innate and adaptive immune response. [Proc Natl Acad Sci USA] Abstract

TMEM203 Is a Binding Partner and Regulator of STING-Mediated Inflammatory Signaling in Macrophages

Scientists report that TMEM203, a conserved putative transmembrane protein, was an intracellular regulator of STimulator of IFN Genes (STING)-mediated signaling. They showed that TMEM203 interacted, functionally cooperated, and comigrated with STING following cell stimulation, which in turn led to the activation of the kinase TBK1, and the IRF3 transcription factor. [Proc Natl Acad Sci USA] Full Article

DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade

Investigators demonstrated that DUX4 expression blocked interferon-γ-mediated induction of major histocompatibility complex (MHC) class I, implicating suppressed antigen presentation in DUX4-mediated immune evasion. [Dev Cell] Abstract | Press Release | Graphical Abstract

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Functional Interactions between Innate Lymphoid Cells and Adaptive Immunity

The authors summarize the current understanding of functional interactions between innate lymphoid cells and the adaptive immune system, discuss limitations and future areas of investigation, and consider the potential for these interactions to be therapeutically harnessed to benefit human health. [Nat Rev Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the immune regulation research field.

Jounce Therapeutics Announces Update on Strategic Collaboration with Celgene Corporation

Jounce Therapeutics, Inc. announced an update on its strategic collaboration with Celgene Corporation, originally established in July 2016. [Jounce Therapeutics, Inc.] Press Release

Synthorx Initiates Patient Dosing in Australia and Announces Clearance of IND in the US for Lead Immuno-Oncology Product Candidate, THOR-707

Synthorx, Inc. announced it has opened HAMMER, a global, Phase I/II, first-in-human clinical trial of THOR-707, with Australia being the first region to enroll patients to date. [Synthorx, Inc.] Press Release

Resolve Therapeutics Announces Completion of Enrollment for Phase IIa Study of RSLV-132 for the Treatment of Lupus

Resolve Therapeutics announced completion of enrollment in its Phase IIa study of RSLV-132 for the treatment of systemic lupus erythematosus. [Resolve Therapeutics (Business Wire, Inc.)] Press Release

Former UK Science Minister Returns as Brexit Government Assembles

The prime minister shake-up sees a return to the Conservative government for Jo Johnson, the prime minister’s brother and a former minister for universities and science. Johnson, who was generally popular with scientists, is back as a minister straddling the Department for Business, Energy and Industrial Strategy — which oversees research — and the Department for Education. [Nature News] Editorial

A Vaunted Program for Boosting the Diversity of US Academic Scientists Is Starting to Spread

Many institutions already operate programs to attract and retain more minorities in STEM fields. But change is occurring at a glacial pace. Overall, black and Hispanic people each make up only about 4% of all tenured faculty at US PhD-granting institutions, percentages that have remained nearly flat for each group since 2013. And the numbers appear to be worse within the STEM disciplines. [ScienceInsider] Editorial

Mexico’s New President Shocks Scientists with Budget Cuts and Disparaging Remarks

A package of harsh austerity measures implemented, has had a deep impact on federally funded laboratories and institutes; it includes a 30% cut to fuel for vehicles and office supplies and a 50% cut to international travel funds and payments to contract workers. Scientists say the cuts are a serious threat to the future of Mexican research. [ScienceInsider] Editorial

NEW British Society for Immunology Congress 2019
December 2-5, 2019
Liverpool, United Kingdom

Visit our events page to see a complete list of events in the community.

NEW Scientific Communications Coordinator (STEMCELL Technologies Inc.)

NEW Postdoctoral Fellow – Quantitative Microscopy of Immune Cells (National Institute on Aging)

NEW Associate or Full Professor – Neuro-Immune/Neuro-Pharmacological Interactions (University of Pennsylvania)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Human Immunology (STEMCELL Technologies Inc.)

Research Associate – Immune Cell Culture (STEMCELL Technologies Inc.)

Postdoctoral Fellow – TCR Immunology/Immune Therapy (The University of Texas MD Anderson Cancer Center)

Postdoctoral Position – Mucosal Immunology (University of California, San Diego)

Senior Scientist – Immuno-Oncology of Hematologic Malignancies (University of Kansas School of Medicine)

Postdoctoral Research Scientist – Molecular Immunology (Babraham Institute)

PhD Scholarships – Systems Biology in Immune and Infectious Diseases (University of Perugia)

Postdoctoral Position – Genetics & Immunology (Columbia University Medical Center)

Postdoctoral Position – Immunology of Enteric Infections (University of Utah)

Assistant, Associate, or Full Professor – Cancer Immunotherapy/Tumor Immunology (University of California, Irvine)

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