Immune Regulation News Volume 12.11 | Mar 27 2020

TOP STORY

A Conserved Dendritic-Cell Regulatory Program Limits Antitumor Immunity

Using single-cell RNA sequencing in human and mouse non-small-cell lung cancers, researchers identified a cluster of dendritic cells (DCs) that they named ‘mature DCs enriched in immunoregulatory molecules’, owing to their co-expression of immunoregulatory genes and maturation genes. [Nature] Abstract

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Glutathione Restricts Serine Metabolism to Preserve Regulatory T Cell Function

Using mice with Treg-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), investigators showed that glutathione loss in Tregs altered serine import and synthesis and that the integrity of this feedback loop was critical for Treg suppressive capacity. Although Gclc ablation did not impair Treg differentiation, mutant mice exhibited severe autoimmunity and enhanced anti-tumor responses. [Cell Metab] Abstract | Graphical Abstract

Microbiota-Derived Metabolites Suppress Arthritis by Amplifying Aryl-Hydrocarbon Receptor Activation in Regulatory B Cells

The authors demonstrated that rheumatoid arthritis patients and arthritic mice had a reduction in microbial-derived short-chain fatty acids (SCFAs) compared to healthy controls and that in mice, supplementation with the SCFA butyrate reduced arthritis severity. [Cell Metab] Abstract | Graphical Abstract

Runx-Mediated Regulation of CCL5 via Antagonizing Two Enhancers Influences Immune Cell Function and Anti-Tumor Immunity

Researchers identified two stage-specific enhancers: the proximal enhancer mediated the constitutive CCL5 expression during the steady state, while the distal enhancer located 1.35-Mb from the promoter induced CCL5 expression in activated cells. [Nat Commun] Full Article

HKDC1 C-Terminal Based Peptides Inhibit Extranodal Natural Killer/T-Cell Lymphoma by Modulation of Mitochondrial Function and EBV Suppression

Investigators showed that hexokinase domain component 1 (HKDC1) was highly upregulated in extranodal nasal-type natural killer/T-cell lymphoma (ENKTL) cells and HKDC1 knockdown significantly suppressed ENKTL tumor growth. In addition, HKDC1 was highly identical with four other hexokinase isoforms, with the only difference being in the last eight amino acids at the C-terminal. [Leukemia] Full Article

Lymph Node Stromal Cells Generate Antigen-Specific Regulatory T Cells and Control Autoreactive T and B Cell Responses

Mechanistically, lymph node stromal cells expressed and presented self-antigens in major histocompatibility complex class II, leading to the conversion of naive CD4⁺ T cells into Treg cells in an IL-2-dependent manner. [Cell Rep] Full Article | Graphical Abstract

CD137 Signaling Regulates Acute Colitis via RALDH2-Expressing CD11b⁻CD103⁺ DCs

Scientists showed that CD137 signaling, specifically in intestinal CD11b⁻CD103⁺ dendritic cells (DCs), restricted acute colitis progression. Mechanistically, CD137 engagement activated TAK1 and subsequently stimulated the AMPK-PGC-1α axis to enhance expression of the Aldh1a2 gene encoding the retinoic acid metabolizing enzyme RALDH2. [Cell Rep] Full Article | Graphical Abstract

Noncanonical STAT1 Phosphorylation Expands Its Transcriptional Activity into Promoting LPS-Induced IL-6 and IL-12p40 Production

In human macrophages, toll-like receptor 4 (TLR4) endocytosis activated a noncanonical phosphorylation of STAT1 at Thr749, which subsequently promoted the production of IL-6 and IL-12p40 through distinct mechanisms. [Sci Signal] Abstract

Low-Dose 17α-Ethinyl Estradiol (EE) Exposure Exacerbates Lupus Renal Disease and Modulates Immune Responses to TLR7/9 Agonists in Genetically Autoimmune-Prone Mice

The authors exposed autoimmune-prone female MRL/lpr mice to a human-relevant dose of EE through the oral route of exposure. Since lupus patients are prone to infections, groups of mice were injected with viral or bacterial surrogates. [Sci Rep] Full Article

Mucosal Delivery of CpG-ODN Mimicking Bacterial DNA via the Intrapulmonary Route Induces Systemic Antimicrobial Immune Responses in Neonatal Chicks

CpG-ODN or saline was delivered via the intrapulmonary route to day-old chicks using a compressor nebulizer in an acrylic chamber. In the first part of the study, two days after mucosal CpG-ODN delivery, 40 chicks from each group were challenged subcutaneously with 1×10⁵ cfu or 1×10⁶ cfu of E. coli and the mortality pattern was monitored for seven days. [Sci Rep] Full Article

The Agpat4/LPA Axis in Colorectal Cancer Cells Regulates Antitumor Responses via p38/p65 Signaling in Macrophages

Mechanistically, Agpat4 silencing-induced lysophosphatidic acid (LPA) release from colorectal cancer cells and polarized macrophages to an M1-like phenotype through LPA receptors 1 and 3. [Signal Transduct Target Ther] Full Article

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Extra-Adrenal Glucocorticoid Biosynthesis: Implications for Autoimmune and Inflammatory Disorders

The authors emphasize that dysregulation of extra-adrenal glucocorticoid production can play a key role in a variety of autoimmune diseases including multiple sclerosis, lupus erythematosus, rheumatoid arthritis, and skin inflammatory disorders such as psoriasis and atopic dermatitis. [Genes Immun] Abstract

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aTyr Pharma and Its Hong Kong Subsidiary, Pangu BioPharma, Announce Government Grant to Fund Bispecific Antibody Development Platform

aTyr Pharma, Inc. announced that the company’s Hong Kong subsidiary, Pangu BioPharma Limited, together with the Hong Kong University of Science and Technology, has been awarded a grant of approximately $750,000 to build a high-throughput platform for the development of bi-specific antibodies. [aTyr Pharma, Inc.] Press Release

Allakos Announces Positive Phase I Results with Antolimab (AK002) in Mast Cell Gastrointestinal Disease

Allakos, Inc. reported results from a Phase I study evaluating the safety and efficacy of antolimab for the treatment of patients with mast cell gastrointestinal disease. [Allakos, Inc. (GlobeNewswire, Inc.)] Press Release

Tens of Thousands of Scientists Are Redeploying to Fight Coronavirus

As labs shut down around the world, researchers are finding creative ways to donate their time, supplies and expertise. [Nature News] Editorial

Universities Issue Hiring Freezes in Response to COVID-19

Numerous universities have made announcements about the suspension of hiring, including Miami University of Ohio, Wright State University, Villanova University, the University of Nevada, Reno, Indiana University, and the University of Auckland in New Zealand, which cites the travel ban affecting Chinese students as one of the main causes of its freeze. [The Scientist] Editorial

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

NEW Postdoctoral Researcher – Intestinal Tissue Regeneration (Karolinska Institutet)

NEW 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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