Immune Regulation News Volume 12.04 | Feb 7 2020

TOP STORY

Interleukin-17A Serves a Priming Role in Autoimmunity by Recruiting IL-1β-Producing Myeloid Cells that Promote Pathogenic T Cells

The authors found that IL-17A-defective mice or mice treated with anti-IL-17A at induction of experimental autoimmune encephalomyelitis (EAE) were resistant to disease and have defective priming of IL-17-secreting γδ T cells and Th17 cells. However, T cells from Il17a^-/- mice induced EAE in wild-type mice following in vitro culture with autoantigen, IL-1β, and IL-23. [Immunity] Abstract | Graphical Abstract

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Methionine Metabolism Shapes T Helper Cell Responses through Regulation of Epigenetic Reprogramming

Using metabolomics, researchers showed that methionine was rapidly taken up by activated T cells and served as the major substrate for biosynthesis of the universal methyl donor S-adenosyl-L-methionine (SAM). Methionine was required to maintain intracellular SAM pools in T cells. [Cell Metab] Abstract | Graphical Abstract

Persistence of Adoptively Transferred T Cells with a Kinetically Engineered IL-2 Receptor Agonist

Investigators report that ACT supported by NKTR-214 increased the proliferation, homing and persistence of anti-tumor T cells compared to ACT with IL-2, resulting in superior anti-tumor activity in a B16-F10 murine melanoma model. The use of NKTR-214 increased the number of polyfunctional T cells in murine spleens and tumors compared to IL-2, and enhanced the polyfunctionality of T and NK cells in the peripheral blood of patients receiving NKTR-214 in a Phase I trial. [Nat Commun] Full Article

Regulation of Heterotopic Ossification by Monocytes in a Mouse Model of Aberrant Wound Healing

The authors examined, using a mouse model of trauma-induced heterotopic ossification, the local microenvironment of the initial post-injury inflammatory response. Single cell transcriptome analyses identified distinct monocyte/macrophage populations at the injury site, with their dynamic changes over time elucidated using trajectory analyses. [Nat Commun] Full Article

An Ontogenetic Switch Drives the Positive and Negative Selection of B Cells

Investigators showed that a B cell intrinsic switch between positive and negative selection during ontogeny is determined by a change from Lin28b to let-7 gene expression. Ectopic expression of a Lin28b transgene in murine B cells restored the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. [Proc Natl Acad Sci USA] Full Article

Microglial A20 Protects the Brain from CD8 T-Cell-Mediated Immunopathology

Scientists showed that microglial A20 was crucial for maintaining brain homeostasis. Without microglial A20, CD8⁺ T cells spontaneously infiltrated the central nervous system and acquired a viral response signature. [Cell Rep] Full Article | Graphical Abstract

Distinct Transcriptional Responses across Tissue-Resident Macrophages to Short-Term and Long-Term Metabolic Challenge

Researchers investigated tissue-resident components of the innate immune system and their response to short- and long-term nutritional challenges. They analyzed the transcriptomes of six tissue-resident macrophage populations upon acute feeding and identify adipose tissue macrophages and the IL-1 pathway as early sensors of metabolic changes. [Cell Rep] Full Article | Graphical Abstract

C3a Elicits Unique Migratory Responses in Immature Low-Density Neutrophils

Scientists demonstrated that pro-metastatic immature low-density neutrophils (iLDNs) more efficiently accumulated in the livers of mice bearing metastatic lesions compared with anti-metastatic mature high-density neutrophils (HDNs). Transcriptomic analyses revealed enrichment of a migration signature in iLDNs relative to HDNs. [Oncogene] Abstract

Low-Dose Interleukin-2 Reverses Behavioral Sensitization in Multiple Mouse Models of Headache Disorders

In a mouse model of chronic migraine, the authors observed that repeated nitroglycerin administration doubled the number of CD3⁺ T cells in the trigeminal ganglia without altering the number of Treg cells, suggesting a deficiency in Treg-mediated immune homeostasis. [Pain] Abstract

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Immune Crosstalk in Cancer Progression and Metastatic Spread: A Complex Conversation

The authors review the evidence of aberrant immune cell crosstalk in metastasis formation and the role that primary tumors play in hijacking these interactions in order to enhance their metastatic potential. They highlight the intriguing parallels between the inflammatory pathways underlying inflammatory disorders and cancer progression. [Nat Rev Immunol] Abstract

T Cell Co-Stimulation and Functional Modulation by Innate Signals

STING signaling inhibits cell growth and stimulates type I interferon responses in T cells through reciprocal regulation between T cell receptor and STING signals. Investigators propose a model whereby innate signals by Toll-like receptors and STING regulate TCR signals and T cell functions. [Trends Immunol] Abstract

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RINVOQ™ (Upadacitinib) Meets Primary and Key Secondary Endpoints in Phase III Study in Psoriatic Arthritis

AbbVie announced positive top-line results from the Phase 3 SELECT-PsA 1 clinical trial. In this study, both doses of RINVOQTM met the primary endpoint of ACR20 response at week 12 versus placebo in adult patients with active psoriatic arthritis who have responded inadequately or are intolerant to one or more non-biologic disease modifying anti-rheumatic drugs. [should be AbbVie] Press Release

Can-Fite Completes 50% Patient Enrollment in Phase III Rheumatoid Arthritis Study and Implements Interim Analysis

Can-Fite BioPharma Ltd. announced it has completed enrollment of approximately 50% of the 525 patients planned for its Phase III ACRobat™ trial to evaluate its drug candidate Piclidenoson as a first-line treatment for rheumatoid arthritis. [Can-Fite BioPharma Ltd.] Press Release

Alkahest Initiates a Phase II Clinical Trial of AKST4290 in Parkinson’s Disease with Funding from the Michael J. Fox Foundation

Alkahest, Inc. announced the dosing of the first patient in a Phase II clinical trial of AKST4290, an orally administered CCR3 inhibitor, for treatment of Parkinson’s disease. The trial, AKST4290-211, is funded in part by The Michael J. Fox Foundation for Parkinson’s Research and will evaluate the effect of AKST4290 on motor function and activities of daily living in patients with Parkinson’s disease. [Alkahest, Inc. (GlobeNewswire, Inc.)] Press Release

Why Did a Chinese University Hire Charles Lieber to Do Battery Research?

Among the ongoing mysteries surrounding last week’s arrest of Harvard University nanoscientist Charles Lieber is the precise nature of the research program Lieber was conducting in his cooperation with Chinese researchers. [ScienceInsider] Editorial

Cash from Cannabis Companies Creates Conflicted Researchers

Imagine that scientists charged with doing research on tobacco’s health implications were funded by tobacco companies. In fact, the tobacco industry used this tactic for decades to cast doubt on the adverse health effects of smoking. But today it would be an outrageous conflict of interest – research on addictive drugs shouldn’t be paid for by people who stand to profit from selling them. Yet this is exactly what is happening with cannabis. [STAT News] Editorial

NEW Keystone Symposia: Tumor Metabolism
March 8-12, 2020
Banff, Alberta, Canada

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NEW Program Manager – Research Infitiatives on Neurofibromatosis (Johns Hopkins University)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Fellowships – Immunology (University of Oslo)

Postdoctoral Researcher – Immunoregulation (GlaxoSmithKline plc.)

Postdoctoral Scientist – Granuloma (Texas Biomedical Research Institute)

Faculty Position – Ion Channels and Immunology (NYU School of Medicine)

Biologist – Aging (NIH National Institute on Aging)

Postdoctoral Fellowship – Immunology (Stanford University)

Tenure Track Position – Genetics/Genomics/Pharmacogenomics of Immune Function in Disease (University of Kentucky)

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