Immune Regulation News Volume 12.12 | Apr 3 2020

TOP STORY

Beta Cell-Specific CD8⁺ T Cells Maintain Stem Cell Memory-Associated Epigenetic Programs during Type 1 Diabetes

Investigators established a DNA methylation-based T cell ‘multipotency index’ and found that beta cell-specific CD8⁺ T cells retained a stem-like epigenetic multipotency score. Single-cell assay for transposase-accessible chromatin using sequencing confirmed the coexistence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8⁺ T cells. [Nat Immunol] Abstract | Press Release

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Sestrins Induce Natural Killer Function in Senescent-Like CD8⁺ T Cells

Researchers found that CD27-CD28-CD8⁺ T cells lost the signaling activity of the T cell antigen receptor and expressed a protein complex containing the agonistic NK receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. [Nat Immunol] Abstract

Integrin α6 Mediates Drug Resistance of Acute Lymphoblastic B-Cell Leukemia

The authors showed that the anti-human α6-blocking antibody P5G10 induced apoptosis in primary acute lymphoblastic leukemia (ALL) in vitro and sensitized primary ALL cells to chemotherapy or tyrosine kinase inhibition in vitro and in vivo. [Blood] Abstract

TNIK Signaling Imprints CD8⁺ T Cell Memory Formation Early after Priming

Scientists analyzed the role of the TRAF2^–/NCK-interacting kinase (TNIK), a signaling molecule downstream of the tumor necrosis factor superfamily receptors such as CD27, in the regulation of CD8⁺ T cell fate during acute infection with lymphocytic choriomeningitis virus. [Nat Commun] Full Article

Regulatory T Cells Confer a Circadian Signature on Inflammatory Arthritis

Researchers showed that the amplitude of intrinsic oscillators within macrophages and neutrophils was limited by the chronic inflammatory environment, suggesting that rhythms in inflammatory mediators might not be a direct consequence of intrinsic clocks. Anti-inflammatory Treg cells within the joints showed diurnal variation, with numbers peaking during the nadir of inflammation. [Nat Commun] Full Article

Divergent Roles for Macrophage C-Type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response

Investigators showed that during colitis, the loss of dectin-1 on myeloid cells prevented intestinal inflammation, while the lack of mannose receptor (MR) exacerbated it. A marked increase in dectin-1 expression in dextran sulfate sodium-exposed MR-deficient mice supports the critical contribution of dectin-1 to colitis outcome. [Cell Rep] Full Article | Graphical Abstract

SPHK2-Generated S1P in CD11b⁺ Macrophages Blocks STING to Suppress the Inflammatory Function of Alveolar Macrophages

Scientists demonstrated that monocyte-derived macrophages recruited into the airspace upregulated the anti-inflammatory function of alveolar macrophages by suppressing their stimulator of type 1 interferon gene (STING) signaling. [Cell Rep] Full Article | Graphical Abstract

The Regulatory Network among CircHIPK3, LncGAS5, and miR-495 Promotes Th2 Differentiation in Allergic Rhinitis

The differential expressions of several circRNAs and lncRNAs were compared in nasal mucosa samples of allergic rhinitis (AR) patients and mice with experimentally induced AR as compared to healthy controls. The results showed that the highly expressed CircHIPK3 and LncGAS5 promoted Th2 differentiation of ovalbumin-induced CD4⁺ T cells and aggravated nasal symptoms of AR mice. [Cell Death Dis] Full Article

NF-κB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia

Researchers generated double-mutant mice, harboring conventional knock-out mutation of NF-κB1/p50 on the genetic background of a transgenic model of Notch-dependent T-cell acute lymphoblastic leukemia (T-ALL). The immunophenotyping of double-mutant mice demonstrated that NF-κB1 deletion inhibited the progression of T-ALL and strongly modified immune-environment of the disease. [Front Immunol] Full Article

Modification of Adenovirus Vaccine Vector-Induced Immune Responses by Expression of a Signaling Molecule

The modification of T-cell and antibody responses induced by TRAM was assessed in vivo in mice and in primates. Co-expression of TRAM and an antigen from adenoviruses increased the transgene-specific CD8⁺ T cell responses in mice. [Sci Rep] Full Article

3′-Sialyllactose Prebiotics Prevents Skin Inflammation via Regulatory T Cell Differentiation in Atopic Dermatitis Mouse Models

Scientists investigated the effect of 3′-aialyllactose (3′-SL) on Treg responses in atopic dermatitis (AD) pathogenesis. Oral administration of 3′-SL reduced AD-like symptoms such as ear, epidermal, and dermal thickness in repeated topical application of house dust mites and 2,4-dinitrochlorobenzene. [Sci Rep] Full Article

Identification of a Nerve-Associated, Lung-Resident Interstitial Macrophage Subset with Distinct Localization and Immunoregulatory Properties

The authors report an interstitial subset of CD169⁺ lung-resident macrophages that were transcriptionally and developmentally distinct from alveolar macrophages. They were primarily localized around the airways and were found in close proximity to the sympathetic nerves in the bronchovascular bundle. [Sci Immunol] Abstract

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Helper-Like Innate Lymphoid Cells in Humans and Mice

The authors summarize the latest research on innate lymphoid cell (ILC) development and plasticity in humans and mice, focusing on the pathogenic role of helper-like ILCs in inflammatory disorders, such as asthma, Crohn’s disease, and rheumatoid arthritis. [Trends Immunol] Abstract

Cancer Epigenetics, Tumor Immunity, and Immunotherapy

Investigators discuss epigenetic regulators of the cancer-immunity cycle and current advances in developing epigenetic therapies to boost anticancer immune responses, either alone or in combination with current immunotherapies. [Trends Cancer] Abstract

Neutrophil Chemoattractant Receptors in Health and Disease: Double-Edged Swords

The expression levels of chemoattractant receptors are dependent on the level of neutrophil maturation and state of activation, with a pivotal modulatory role for the (inflammatory) environment. Scientists provide an overview of chemoattractant receptors expressed by neutrophils in health and disease. [Cell Mol Immunol] Abstract

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Emerald Health Pharmaceuticals Initiates Phase II Clinical Study in Systemic Sclerosis

Emerald Health Pharmaceuticals, Inc. has initiated a Phase IIa international clinical study for the treatment of patients with systemic sclerosis (SSc), a severely debilitating and life-threatening form of scleroderma. [Emerald Health Pharmaceuticals, Inc.] Press Release

Pfizer Receives European Approval for Oncology Biosimilar, RUXIENCE™ (Rituximab)

Pfizer, Inc. announced that the European Commission has approved RUXIENCE™, a monoclonal antibody and biosimilar to MabThera^®, for the treatment of non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis with polyangiitis and microscopic polyangiitis, and pemphigus vulgaris. [Pfizer, Inc.] Press Release

Female Scientists Allege Discrimination, Neglect of Research on Women at NIH’s Child Health Institute

In November 2014, nine senior female scientists at the National Institute of Child Health and Human Development requested a meeting with their director. Their concern: that the careers of women at the institute’s Division of Intramural Research were being stymied by its powerful scientific director, Constantine Stratakis. [ScienceInsider] Editorial

Americans Are Underestimating How Long Coronavirus Disruptions Will Last, Health Experts Say

Public health experts are increasingly worried that Americans are underestimating how long the coronavirus pandemic will disrupt everyday life in the country, warning that the Trump administration’s timelines are offering many a false sense of comfort. [STAT News] Editorial

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NEW 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)

Research Specialist – Immune Cell Function (Johns Hopkins University)

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

Postdoctoral Fellow – Molecular Mechanisms of Inflammation (Universitätsklinikum Jena)

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

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

Postdoctoral Fellowships – Immunology (University of Oslo)

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