Immune Regulation News Volume 12.14 | Apr 24 2020

TOP STORY

New Therapeutic Options for Multiple Sclerosis in Sight

Strategies for treating multiple sclerosis have so far focused primarily on T and B cells. A group of Max DelBruck researchers has now unveiled a new approach in Nature Immunology – one that seeks to increase treatment effectiveness by selectively targeting another type of immune cell called monocytes. [Max DelBruck Center for Molecular Medicine] Press Release | Abstract

(Ranked by impact factor of the journal)

Overcoming Wnt-β-Catenin Dependent Anticancer Therapy Resistance in Leukemia Stem Cells

Mechanistically, β-catenin bound multiple immune-checkpoint gene loci, and targeted doxorubicin treatment inhibited expression of multiple immune checkpoints specifically in leukemia stem cells, including PD-L1, TIM3 and CD24. [Nat Cell Biol] Abstract

The Platelet Receptor CLEC-2 Blocks Neutrophil Mediated Hepatic Recovery in Acetaminophen Induced Acute Liver Failure

Researchers demonstrated that blocking platelet CLEC-2 signaling enhanced liver recovery from acute toxic liver injuries by increasing tumor necrosis factor-α production which then enhanced reparative hepatic neutrophil recruitment. [Nat Commun] Full Article

Ethanol Consumption Inhibits T_FH Cell Responses and the Development of Autoimmune Arthritis

Investigators showed that alcohol and its metabolite acetate altered the functional state of T follicular helper (T_FH) cells in vitro and in vivo, thereby exerting immune regulatory and tolerance-inducing properties. [Nat Commun] Full Article

AAV-CRISPR Gene Editing Is Negated by Pre-Existing Immunity to Cas9

Scientists tested in a mouse model whether pre-existing immunity to Streptococcus pyogenes (SaCas9) would pose a barrier to liver genome editing with AAV packaging CRISPR/Cas9. Although efficient genome editing occurred in mice liver with pre-existing SaCas9 immunity, this was accompanied by an increased proportion of CD8⁺ T-cells in the liver. [Mol Ther] Abstract | Full Article | Graphical Abstract

CytoMAP: A Spatial Analysis Toolbox Reveals Features of Myeloid Cell Organization in Lymphoid Tissues

The authors applied histo-cytometric multidimensional analysis pipeline (CytoMAP) to study the microanatomy of innate immune subsets in murine lymph nodes (LNs) and revealed mutually exclusive segregation of migratory dendritic cells (DCs), regionalized compartmentalization of SIRPα⁻ dermal DCs, and preferential association of resident DCs with select LN vasculature. [Cell Rep] Full Article | Graphical Abstract

Cathepsin S Alterations Induce a Tumor-Promoting Immune Microenvironment in Follicular Lymphoma

Scientists provide biochemical, structural, functional, and clinical evidence that Cathepsin S alterations induced a tumor-promoting immune microenvironment in follicular lymphoma. [Cell Rep] Full Article | Graphical Abstract

Default Polyfunctional T Helper 1 Response to Ample Signal 1 Alone

Using cell-based vaccines, researchers selectively amplified signal 1 by exclusive presentation of an optimized peptide:MHC II complex in the absence of classic costimulation. Contrary to expectations, amplified signal 1 alone was strongly immunogenic and selectively expanded high-affinity T cell receptors (TCR) clonotypes, despite delivering intense TCR signals. [Cell Mol Immunol] Full Article

The Functions of IL-23 and IL-2 on Driving Auto-Immune Effector T-Helper 17 Cells into the Memory Pool in Dry Eye Disease

Using a murine model of dry eye disease, scientists detected a linear transition from effector-to-memory T-helper 17 cells during the abatement phase of acute inflammation, which was accompanied by persistently high levels of IL-23 and diminished levels of IL-2. [Mucosal Immunol] Abstract

Novel, Non-Gene-Destructive Knock-In Reporter Mice Refute the Concept of Monoallelic Gata3 Expression

The authors generated a novel strain of knock-in reporter mice, termed GATIR, by inserting an expression cassette encoding a bright fluorescent marker into the 3′-untranslated region of the endogenous Gata3 locus. [J Immunol] Full Article

Smooth-Muscle-Derived WNT5A Augments Allergen-Induced Airway Remodeling and Th2 Type Inflammation

WNT5A increased mucus production, and enhanced eosinophilic infiltration and serum IgE production in ovalbumin-treated animals. CD4⁺ T cells of asthma patients and healthy controls were stimulated with WNT5A and changes in gene transcription assessed by RNA-seq. [Sci Rep] Full Article

Deficiency of CD44 Prevents Thoracic Aortic Dissection in a Murine Model

Investigators examined the role of CD44 in the development of thoracic aortic dissection (TAD). TAD was induced by the continuous infusion of β-aminopropionitrile, a lysyl oxidase inhibitor, and angiotensin II for seven days in wild type mice and CD44 deficient mice. [Sci Rep] Full Article

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Non-Canonical Cell Fate Regulation by Bcl-2 Proteins

The authors discuss the mechanisms through which Bcl-2 proteins influence cell fate as they regulated autophagy, cellular senescence, inflammation, bioenergetic metabolism, Ca²⁺ fluxes, and redox homeostasis. [Trends Cell Biol] Abstract

Translating IL-6 Biology into Effective Treatments

Investigators discuss the history of research into IL-6 biology and the development of therapies that target IL-6 signaling, including the successes and challenges and with an emphasis on rheumatic diseases. [Nat Rev Rheumatol] Full Article

Emerging Role of PTEN Loss in Evasion of the Immune Response to Tumors

Scientists summarize findings that demonstrate how the loss of PTEN function elicited specific changes in the immune response in several types of cancer. They also discuss ongoing clinical trials that illustrate the potential utility of PTEN as a predictive biomarker for immune checkpoint blockade therapies. [Br J Cancer] Abstract

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

Cue Biopharma Announces Clinical Trial Collaboration Agreement with Merck to Evaluate CUE-101 in Combination with KEYTRUDA^® (Pembrolizumab) as First-Line Treatment for HPV⁺ Recurrent/Metastatic Head and Neck Cancer

Cue Biopharma, Inc. announced it has entered into a clinical collaboration agreement with Merck, through a subsidiary, to evaluate the combination of Cue Biopharma’s investigational product candidate CUE-101, a first-in-class biologic, with Merck’s anti-PD-1 therapy, KEYTRUDA^® in patients with advanced head and neck cancer. [Cue Biopharma, Inc] Press Release

Sanofi Brain-Penetrant BTK Inhibitor Significantly Reduced Disease Activity in Phase II Trial in Relapsing Multiple Sclerosis

Sanofi’s investigational Bruton’s tyrosine kinase (BTK) inhibitor, an oral, brain-penetrant, selective small molecule achieved both the primary and secondary endpoints in a Phase IIb trial evaluating efficacy and safety in participants with relapsing forms of multiple sclerosis. The BTK inhibitor significantly reduced disease activity associated with multiple sclerosis as measured by magnetic resonance imaging. [Sanofi] Press Release

Arcutis Announces Enrollment of First Patient in Phase I/IIb Study of ARQ-252 in Patients with Chronic Hand Eczema

Arcutis Biotherapeutics, Inc. announced that it has enrolled the first patient in Phase I/IIb study of ARQ-252, a potent and highly selective topical small molecule inhibitor of janus kinase type 1, in adult patients with chronic hand eczema. [Arcutis Biotherapeutics, Inc.] Press Release

Open Science Takes On the Coronavirus Pandemic

When reports emerged in late 2019 of an outbreak of a new coronavirus centred in Wuhan, China, researchers at the virological-analysis website Nextstrain were ready. The open-source project tracks the spread of viruses through genetic variations in the sequences that scientists find. [Nature News] Editorial

Untapped Potential: More US Labs Could Be Providing Tests for Coronavirus

A survey of more than 4,000 researchers in the United States suggests that better coordination at an institutional and national level could make hundreds of thousands more tests for coronavirus available. [Nature News] Editorial

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NEW Postdoctoral Researcher – Immune Checkpoint Therapy (Canadian Nuclear Laboratories)

Postdoctoral Researcher – Cancer Treatment Sensitivty (Johannes Kepler University of Linz)

Chair – Department of Microbiology and Immunology (Western University)

Postdoctoral Fellow – Acute Myeloid Leukemia (Icahn School of Medicine at Mount Sinai)

Senior Scientist – Immunotherapy and Transplant Rejection (Regensburg Center for Interventional Immunology)

Postdoctoral Researcher – Intestinal Tissue Regeneration (Karolinska Institutet)

Principle Scientist – Cancer and Auto-Immune Disorders (Sanofi)

Postdoctoral Fellow – Mucosal Immunology and Allergies (University of Michigan)

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

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

Postdoctoral Fellowships – Immunology (University of Oslo)

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