Immune Regulation News Volume 9.45 | Nov 24 2017

TOP STORY

Diabetes: Immune System Can Regulate Insulin

Inflammation processes are responsible for the failure of insulin production in diabetes patients. The patients’ own immune systems can contribute to treatment of this disease: researchers found a feedback mechanism that could help maintain insulin production in overweight sufferers. [Press release from the University of Basel discussing online prepublication in Immunity] Press Release | Abstract | Graphical Abstract

(Ranked by impact factor of the journal)

Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis

The authors investigated the metabolic demands of migrating Treg cells in vitro and in vivo. They showed that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase. [Immunity] Full Article | Press Release | Graphical Abstract

PD-L1 Genetic Overexpression or Pharmacological Restoration in Hematopoietic Stem and Progenitor Cells Reverses Autoimmune Diabetes

Transcriptomic profiling of hematopoietic stem and progenitor cells revealed that cells are deficient in programmed death ligand 1 (PD-L1), an important immune checkpoint, in the type 1 diabetes nonobese diabetic mouse model. Notably, the immunoregulatory molecule PD-L1 played a determinant role in controlling/inhibiting activated T cells and thus maintains immune tolerance. [Sci Transl Med] Abstract | Press Release 1 | Press Release 2 | Editorial

TCR Engagement Negatively Affects CD8 but Not CD4 CAR T Cell Expansion and Leukemic Clearance

Using an immunocompetent, syngeneic murine model of CD19-targeted CAR T cell therapy for pre–B cell acute lymphoblastic leukemia in which the CAR is introduced into T cells with known TCR specificity, researchers demonstrated loss of CD8 CAR T cell efficacy associated with T cell exhaustion and apoptosis when T cell receptor (TCR) antigen is present. [Sci Transl Med] Abstract

A Structurally Distinct TGF-β Mimic from an Intestinal Helminth Parasite Potently Induces Regulatory T Cells

Investigators identified a Heligmosomoides polygyrus TGF-β mimic (Hp-TGM) that replicates the biological and functional properties of TGF-β, including binding to mammalian TGF-β receptors and inducing mouse and human Foxp3⁺ Treg cells. Hp-TGM had no homology with mammalian TGF-β or other members of the TGF-β family, but was a member of the complement control protein superfamily. [Nat Commun] Full Article | Press Release

Regulatory T Cells Control Toxicity in a Humanized Model of IL-2 Therapy

Scientists showed that dose-dependent morbidity and mortality of IL-2 immunotherapy can be modeled in human immune system mice. Depletion of human T cell subsets during the high-dose IL-2 treatment reduced toxicity, pointing to the central function of T cells. [Nat Commun] Full Article

The Aryl Hydrocarbon Receptor Preferentially Marks and Promotes Gut Regulatory T Cells

Investigators generated mouse genetic models to ablate or activate aryl hydrocarbon receptor (Ahr) expression specifically in Tregs. They showed that Ahr was expressed more abundantly by peripherally induced Tregs in the gut and that its expression was independent of microbiota. [Cell Rep] Full Article | Graphical Abstract

Regulatory T Cells Are Expanded by Teriparatide Treatment in Humans and Mediate Intermittent PTH‐Induced Bone Anabolism in Mice

Researchers showed that Teriparatide and intermittent PTH (iPTH) cause a ~two‐threefold increase in the number of Tregs in humans and mice. Attesting in vivo relevance, blockade of the Treg increase in mice prevented the increase in bone formation and trabecular bone volume and structure induced by iPTH. [EMBO Rep] Abstract | Graphical Abstract

The IL-21-mTOR Axis Blocks Treg Differentiation and Function by Suppression of Autophagy in Patients with Systemic Lupus Erythematosus

The authors investigated whether mechanistic target of rapamycin (mTOR) is activated within Tregs and causes their depletion and dysfunction in patients with systemic lupus erythematosus (SLE). SLE Tregs exhibited increased mTOR complex (mTORC)1 and mTORC2 activities but diminished autophagy, GATA-3 and CTLA-4 expression, and suppressor function. IL-21, but not IL-6 or IL-17, blocked Treg development. [Arthritis Rheumatol] Abstract

Interplay of Neuronal and Non-Neuronal Genes Regulates Intestinal DAF-16-Mediated Immune Response during Fusarium Infection of Caenorhabditis elegans

The RNA-seq analysis identified shared and unique signaling pathways regulated by DAF-16/FOXO and SIR-2.1 linking neuronal stress, which facilitated negative regulation of intestinal innate immunity. Genetic analysis revealed that GCY-5 in ASE functions upstream of DAF-16, whereas ASI-specific SRD-1 regulated behavioural immunity. [Cell Death Discov] Full Article

The Similarities between smDCs and regDCs in Alleviating the Immune Injury Caused by Transplantation of Hepatocytes Differentiated from ESCs

The authors investigated the tolerogenic mechanisms induced by semimature dendritic cells (smDCs) and regulatory dendritic cells (regDCs) after transplantation of hepatocytes differentiated from mouse embryonic stem cells (ESCs) and confirmed the low immunogenicity of hepatocytes differentiated from ESCs. [Stem Cell Res Ther] Full Article

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Nerve Stimulation: Immunomodulation and Control of Inflammation

Neuronal stimulation is an emerging field in modern medicine to control organ function and re-establish physiological homeostasis during illness. Recent advances in electroacupuncture may permit activation of specific neuronal networks to prevent organ damage in inflammatory and infectious disorders. [Trends Mol Med] Abstract

Immune Checkpoint Inhibitors in Sarcomas: In Quest of Predictive Biomarkers

The authors provide a brief overview of the mechanisms of action of immune checkpoint inhibitors and discuss the proposed biomarkers of therapy response, such as lymphocytic infiltration, intratumoral PD-L1 expression, and mutational load in sarcomas. [Lab Invest] Abstract

Harnessing the Power of Regulatory T Cells to Control Autoimmune Diabetes: Overview and Perspective

Scientists summarize the current understanding of biomarkers and functions of both Foxp3⁺ Treg and type 1 regulatory T cells in health and in type 1 diabetes, examine the outcome of experimental therapies in both animal models and humans via manipulation of Treg responses, and give an outlook on the potential of Treg-based immunotherapies in the prevention and treatment of this disease. [Immunology] Abstract

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Six Researchers from MD Anderson Elected as AAAS Fellows

Shao-Cong Sun, Ph.D., professor of Immunology, was honored for his contributions to the understanding of NF-kB signaling pathways and the regulation of immune responses and inflammatory diseases by protein ubiquitination. [The University of Texas MD Anderson Cancer Center] Press Release

Janssen Submits Application to U.S. FDA to Expand Indication for DARZALEX^® (Daratumumab) Combination Therapy for Patients with Newly Diagnosed Multiple Myeloma Who Are Transplant Ineligible

Janssen Biotech, Inc. announced that it has submitted a supplemental Biologics License Application to the FDA for DARZALEX^®. This application seeks to expand the current indication, using DARZALEX in combination with bortezomib, melphalan and prednisone for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplantation. [Johnson & Johnson Services, Inc.] Press Release

Nobel Laureates Demand Release of Iranian Scholar Facing Death Sentence

Some 75 Nobel prizewinners have called on the Iranian government to release Ahmadreza Djalali, a researcher in disaster medicine who was sentenced to death last month. The letter is the latest and most powerful protest against the ruling by the scientific community so far. [Nature News] Editorial

Still No Science Advisor at the White House

Ten months into his presidency, Donald Trump has yet to name a science advisor. It’s the longest amount of time a modern president has taken to nominate someone to the position since at least 1976, when Congress established the White House’s Office of Science and Technology Policy. [MIT Technology Review] Editorial

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