Immune Regulation News Volume 12.16 | May 8 2020

TOP STORY

Myeloid PTEN Promotes Chemotherapy-Induced NLRP3-Inflammasome Activation and Anti-Tumor Immunity

Researchers showed that chemotherapy-induced anti-tumor immune responses and tumor suppression relied on myeloid-cell PTEN, which was essential for chemotherapy-induced activation of the NLRP3 inflammasome and antitumor immunity. [Nat Cell Biol] Abstract

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Diversity in Medullary Thymic Epithelial Cells Controls the Activity and Availability of iNKT Cells

Investigators examined medullary thymic epithelial cell heterogeneity and its influence on CD1d-restricted iNKT cells. They found three distinct mTEC^low subsets distinguished by surface, intracellular and secreted molecules, and identified LTβR as a cell-autonomous controller of their development. [Nat Commun] Full Article

N-GSDMD Trafficking to Neutrophil Organelles Facilitates IL-1β Release Independently of Plasma Membrane Pores and Pyroptosis

The authors report that although N-Gasdermin-D (GSDMD) was required for IL-1β secretion in NLRP3-activated human and murine neutrophils, N-GSDMD did not localize to the plasma membrane (PM) or increase PM permeability or pyroptosis. Instead, biochemical and microscopy studies revealed that N-GSDMD in neutrophils predominantly associated with azurophilic granules and LC3⁺ autophagosomes. [Nat Commun] Full Article

Nanocarrier-Mediated Immunogenic Chemotherapy for Triple Negative Breast Cancer

To remodel the tumor microenvironment, researchers developed a liposome formulation to deliver a potential immunogenic cell death inducing agent, 17-(allylamino)-17-demethoxygeldanamycin, in a tumor targeted manner to reverse the immunosuppressive microenvironment and facilitate the checkpoint blockade immunotherapy. [J Control Release] Abstract | Graphical Abstract

Suppression of Inflammasome Activation by IRF8 and IRF4 in cDCs Is Critical for T Cell Priming

Scientists found that conventional DCs (cDCs) suppressed inflammasome activation to prevent pyroptotic cell death, thus preserving their ability to prime both CD4 and CD8 T cells. Transcription factors IRF8 and IRF4, in cDC1s and cDC2s, respectively, mediated suppression of inflammasome activation by limiting the expression of inflammasome-associated genes. [Cell Rep] Full Article | Graphical Abstract

MicroRNA-9 Fine-Tunes Dendritic Cell Function by Suppressing Negative Regulators in a Cell-Type-Specific Manner

Researchers found that the microRNA miR-9 was upregulated in both bone marrow-derived DCs and conventional DC1s but not in conventional DC2s following stimulation. miR-9 expression in BMDCs and conventional DC1s promoted enhanced DC activation and function, including the ability to stimulate T cell activation and control tumor growth. [Cell Rep] Full Article | Graphical Abstract

Microwave Ablation of Primary Breast Cancer Inhibits Metastatic Progression in Model Mice via Activation of Natural Killer Cells

Using two murine models of stage IV breast cancer, investigators found that microwave ablation (MWA) of primary breast cancer inhibited the progression of lung metastasis and improved survival. NK cells were activated after MWA of the primary tumor and exhibited enhanced cytotoxic functions, and the cytotoxic pathways of NK cells were activated. [Cell Mol Immunol] Abstract

Single Cell and Tissue-Transcriptomic Analysis of Murine Bladders Reveals Age- and TNFα-Dependent but Microbiota-Independent Tertiary Lymphoid Tissue Formation

Tissue transcriptomics of unperturbed, young and aged bladders identified a highly altered immune landscape as a fundamental feature of the aging female bladder. Detailed mapping of immune cells using single cell RNA-sequencing revealed novel subsets of macrophages and dendritic cells and unique changes to the immune repertoire in the aged bladder. [Mucosal Immunol] Abstract

Development of a New Macrophage-Specific TRAP Mouse (Mac^TRAP) and Definition of the Renal Macrophage Translational Signature

Scientists adopted a Translational Ribosome Affinity Purification (TRAP)- approach and designed a transgene that expressed an eGFP-tagged ribosomal protein (L10a) under the control of the macrophage-specific c-fms promoter to generate c-fms-eGFP-L10a Mac^TRAP. [Sci Rep] Full Article

Neurons Promote Encephalitogenic CD4⁺ Lymphocyte Infiltration in Experimental Autoimmune Encephalomyelitis

Researchers defined a critical role of excitatory neurons in the pathogenesis of CD4⁺ lymphocyte accumulation in experimental autoimmune encephalitis (EAE). They silenced the activity of excitatory neurons in a mouse model of targeted EAE using inhibitory designer receptors exclusively activated by designer drugs under a CaMKIIα promoter. [Sci Rep] Full Article

Immune-Instructive Polymers Control Macrophage Phenotype and Modulate the Foreign Body Response In Vivo

Unbiased high-throughput screening of a large library of polymer chemistries is undertaken, identifying materials able to instruct macrophage attachment and polarization to pro- or anti-inflammatory phenotypes. The bioinstructive polymer function was validated by a murine model in which modulation of the foreign body response was shown. [Matter] Full Article | Graphical Abstract

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Innate Lymphoid Cells Control Signaling Circuits to Regulate Tissue-Specific Immunity

The authors discuss emerging research on the influence of the nervous system, circadian rhythm, and developmental plasticity on innate lymphoid cell function. [Cell Res] Full Article

The Speckled Protein (SP) Family: Immunity’s Chromatin Readers

Mutations within immune expressed SPs associate with numerous immunological diseases including Crohn’s disease, multiple sclerosis, chronic lymphocytic leukemia, veno-occlusive disease with immunodeficiency, as well as Mycobacterium tuberculosis infection, underscoring their importance in immune regulation. [Trends Immunol] Full Article

How Does Spaceflight Affect the Acquired Immune System?

Investigators summarize and discuss the influence of the spaceflight environment on acquired immunity. Bone marrow and the thymus, two major primary lymphoid organs, were evidently affected by gravitational change during spaceflight. [npj Microgravity] Full Article

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AVROBIO and Magenta Therapeutics Announce Collaboration to Evaluate Targeted Antibody-Drug Conjugate as a Potential Conditioning Regimen for Lentiviral Gene Therapies

AVROBIO, Inc. and Magenta Therapeutics announced a research and clinical collaboration agreement to evaluate the potential utility of MGTA-117, Magenta’s novel targeted antibody-drug conjugate for conditioning patients before they receive one of AVROBIO’s investigational lentiviral gene therapies. [AVROBIO, Inc.] Press Release

Rubius Therapeutics Announces Dosing of First Patient in Phase I/II Trial of RTX-240, an Allogeneic Cellular Therapy, for the Treatment of Solid Tumors

Rubius Therapeutics, Inc. announced that the first patient has been dosed in its Phase I/II clinical trial of RTX-240 for the treatment of patients with relapsed/refractory or locally advanced solid tumors. [Rubius Therapeutics, Inc.] Press Release

How Swamped Preprint Servers Are Blocking Bad Coronavirus Research

Repositories are rapidly disseminating crucial pandemic science — and they’re screening more closely to guard against poor-quality work. [Nature News] Editorial

‘It Will Not Be Easy.’ as Labs Begin to Reopen, Enormous Challenges Remain

One of the biggest challenges labs face is how to keep their members physically distanced to limit any potential spread of SARS-CoV-2. [ScienceInsider] Editorial

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