Immune Regulation News Volume 12.09 | Mar 13 2020

TOP STORY

A Bioorthogonal System Reveals Antitumor Immune Function of Pyroptosis

Researchers established a bioorthogonal chemical system, in which a cancer-imaging probe phenylalanine trifluoroborate that could enter cells desilylated and ‘cleaved’ a designed linker that contained a silyl ether. This system enabled the controlled release of a drug from an antibody-drug conjugate in mice. [Nature] Abstract

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Perivascular Localization of Macrophages in the Intestinal Mucosa Is Regulated by Nr4a1 and the Microbiome

The authors showed by imaging the murine small and large intestines in steady-state that intestinal CX3CR1⁺ macrophages formed an interdigitated network intimately adherent to the entire mucosal lamina propria vasculature. The macrophages formed contacts with each other, which were disrupted in the absence of microbiome, monocyte recruitment, or monocyte conversion. [Nat Commun] Full Article

Suppression of Age-Related Salivary Gland Autoimmunity by Glycosylation-Dependent Galectin-1-Driven Immune Inhibitory Circuits

Investigators demonstrated that aged galectin-1-null mutant mice developed a spontaneous inflammatory process in salivary glands that resembled Sjögren’s syndrome. This spontaneous autoimmune phenotype was recapitulated in mice lacking β1,6N-acetylglucosaminyltransferase V, an enzyme responsible for generating β1,6-branched complex N-glycans, which serve as a major ligand for this lectin. [Proc Natl Acad Sci USA] Abstract

RIPK3 Collaborates with GSDMD to Drive Tissue Injury in Lethal Polymicrobial Sepsis

Scientists found that blockage of both necroptosis and pyroptosis resulted in accumulative protection against septic shock, systemic blood clotting and multi-organ injury in mice. Bone marrow transplantation confirmed that necroptosis and pyroptosis in both myeloid and nonmyeloid cells were indispensable in the progression of sepsis-induced multi-organ injury. [Cell Death Differ] Abstract

Neurokinin-1 Receptor Signaling Is Required for Efficient Ca²⁺ Flux in T-Cell-Receptor-Activated T Cells

The authors showed that the neurokinin-1 receptor (NK1R) and its agonists, the neuropeptides substance P and hemokinin-1, co-localized within the immune synapse during cognate activation of T cells. Simultaneous T cell receptor and NK1R stimulation was necessary for efficient Ca²⁺ flux and Ca²⁺-dependent signaling that sustained the survival of activated T cells and helper 1 (Th1) and Th17 bias. [Cell Rep] Full Article | Graphical Abstract

Anti-Tumor Effects of Anti-PD-1 Antibody, Pembrolizumab, in Humanized NSG PDX Mice Xenografted with Dedifferentiated Liposarcoma

Researchers conducted a pan-cancer tumor data analysis to identify key immune-related variables strongly associated with sarcoma prognosis, and they explored whether these expected factors were functionally correlated with anti-PD-1 therapy in humanized NOD.Cg-Prkdc^scidIl2rg^tm1Wjl/SzJ (NSG) mice xenografted with dedifferentiated liposarcoma. [Cancer Lett] Abstract

Eosinophil Accumulation in Postnatal Lung Is Specific to the Primary Septation Phase of Development

Investigators determined that in mice, mature eosinophils were transiently recruited to the lung during postnatal days 3-14, which specifically corresponded to the primary septation/alveolarization phase of lung development. Developmental eosinophils peaked during P10-14 and exhibited Siglec-F^,ed/highCD11c^-/low phenotypes, similar to allergic asthma models. [Sci Rep] Full Article

Bisphenol a Induces Coronary Endothelial Cell Necroptosis by Activating RIP3/CamKII Dependent Pathway

BPA initiated a cardiac inflammatory response, up-regulation of M1 macrophage polarization, and increased oxidative stress, coinciding with the increased expression of CamKII and the necroptotic effector RIP3. [Sci Rep] Full Article

Self-Assembled Multivalent Aptamer Nanoparticles with Potential CAR-Like Characteristics Could Activate T Cells and Inhibit Melanoma Growth Both In Vitro and In Vivo

Investigators showed that CAR-like multivalent aptamer nanoparticles (X polymers) could recognize both the murine (m)CD28 and mCTLA-4 molecules. Confocal imaging and flow cytometry assay showed that the X polymers could target both T cells and B16 cells in vitro. [Mol Ther Oncolytics] Abstract | Full Article

Obesity Reshapes Visceral Adipose Tissue-Derived MHC I Associated-Immunopeptidomes and Generates Immunogenic Peptides to Drive CD8⁺ T Cell Responses

Researchers conducted in-depth mapping of major histocompatibility complex (MHC) I-associated immunopeptidome (MIP) of visceral adipose tissue (VAT) from lean and obese mice using large-scale high-resolution mass spectrometry, and observed that obesity significantly altered the landscape of VAT MIPs. Additionally, the obese VAT-exclusive MIP source proteome reflected a distinct obesity-associated signature. [iScience] Abstract | Full Article | Graphical Abstract

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Toll-Like Receptors and the Control of Immunity

Investigators describe the mechanisms and consequences of toll-like receptor (TLR)-mediated signal transduction with a focus on themes identified in the TLR pathways that also explain the operation of other immune signaling pathways. These themes include the detection of conserved microbial structures to identify infectious agents and the use of supramolecular organizing centers as signaling organelles that ensure digital cellular responses. [Cell] Abstract

Neuroimmune Connections in Aging and Neurodegenerative Diseases

The authors focus on the impact of CNS-resident cells of the innate immune system for the development of neurodegenerative diseases, review immune pathway genes that have been identified, and discuss the vicious cycle between inflammation and neurodegeneration. [Trends Immunol] Abstract

The Evolving Role of TonEBP as an Immunometabolic Stress Protein

Some of the single-nucleotide polymorphisms (SNPs) in tonicity-responsive enhancer-binding protein (TonEBP) introns are cis-expression quantitative trait loci that affect TONEBP transcription. These SNPs are associated with increased risk of type 2 diabetes mellitus, diabetic nephropathy, inflammation, high blood pressure and abnormal plasma osmolality, indicating that variation in TONEBP expression might contribute to these phenotypes. [Nat Rev Nephrol] Abstract

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

FDA Partially Halts Phase I Study of ACTR707 in Non-Hodgkin Lymphoma

The FDA has placed a partial clinical hold on the Phase I trial of ACTR707 in combination with rituximab in patients with relapsed/refractory B-cell lymphoma from Unum Therapeutics, following the submission of a safety report from the company. [Unum Therapeutics (TargetedOnc 2020 Intellisphere, LLC.)] Press Release

2020 Paul Ehrlich and Ludwig Darmstaedter Prize for Shimon Sakaguchi

Shimon Sakaguchi, professor of Experimental Immunology at Osaka University will receive the 2020 Paul Ehrlich and Ludwig Darmstaedter Prize for his pioneering discoveries of regulatory T cells and their role in self-tolerance. These cells have the potential to become the new heroes of medicine. [Goethe University Frankfurt (EurekAlert!)] Press Release

UK Government to Boost R&D Spending

The British government has announced a 15 percent increase in public funding for research and development as part of its 2020 budget in a move that was generally welcomed by scientists. [The Scientist] Editorial

Universities Are Forging Ties with the FBI as US Cracks Down on Foreign Influence

US universities are forging closer ties with FBI agents, encouraging scientists to disclose foreign sources of research funding, and tightening restrictions on researchers’ travel. [Nature News] Editorial

NEW American Association for Cancer Research (AACR) Annual Meeting 2020
April 24-29, 2020
San Diego, California, United States

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

NEW Research Specialist – Immune Cell Function (Johns Hopkins University)

NEW Assistant Professor – Pharmacology and Cancer Biology (Wayne State University)

NEW Postdoctoral Fellow – Molecular Mechanisms of Inflammation (Universitätsklinikum Jena)

Postdoctoral Fellow – Leukemia Biology and Dendritic Cells (Dana Farber Cancer Institute)

Postdoctoral Position – Leukocyte Extravasation across Postcapillary Venules (University Hospital of Muenster)

Postdoctoral Fellow – Immunometabolism (Braunschweig Univesity of Technology)

Postdoctoral Investigators – Single Cell Genomics (GlaxoSmithKline plc.)

Program Manager – Research Initiatives on Neurofibromatosis (Johns Hopkins University)

Postdoctoral Fellowships – Immunology (University of Oslo)

Postdoctoral Researcher – Immunoregulation (GlaxoSmithKline plc.)

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