Immune Regulation News Volume 12.02 | Jan 24 2020

TOP STORY

Transcriptomic and Epigenetic Mechanisms Underlying Myeloid Diversity in the Lung

Investigators provide systematic evaluation of transcriptomes and open chromatin of alveolar macrophages (AMs), interstitial macrophages (IMs) and lung monocytes from two mouse strains enabled inference of common and cell-specific transcriptional regulators. They provide evidence that these factors drove selection of regulatory landscapes that specified distinct phenotypes of AMs and IMs and entrained qualitatively different responses to toll-like receptor 4 signaling in vivo. [Nat Immunol] Abstract

(Ranked by impact factor of the journal)

Genome-Wide CRISPR-Cas9 Screening Reveals Ubiquitous T Cell Cancer Targeting via the Monomorphic MHC Class I-Related Protein MR1

Researchers used genome-wide CRISPR-Cas9 screening to establish that a T cell receptor (TCR) recognized and killed most human cancer types via the monomorphic MHC class I-related protein, MR1, while remaining inert to noncancerous cells. Unlike mucosal-associated invariant T cells, recognition of target cells by the TCR was independent of bacterial loading. [Nat Immunol] Abstract | Press Release

Genetic Deletion of Mast Cell Serotonin Synthesis Prevents the Development of Obesity and Insulin Resistance

Scientists report that the exposure of mice to thermoneutrality promoted the infiltration of white adipose tissue with mast cells that were highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1^−/− mast cells or selective mast cell deletion of Tph1 enhanced uncoupling protein 1 expression in white adipose tissue and protected mice from developing obesity and insulin resistance. [Nat Commun] Full Article

PTH Induces Bone Loss via Microbial-Dependent Expansion of Intestinal TNF⁺ T Cells and Th17 Cells

Segmented filamentous bacteria⁺ microbiota enabled parathyroid hormone (PTH) to expand intestinal TNF⁺ T and Th17 cells and increased their S1P-receptor-1 mediated egress from the intestine and recruitment to the bone marrow (BM) that caused bone loss. CXCR3-mediated TNF⁺ T cell homing to the BM upregulated the Th17 chemoattractant CCL20, which recruited Th17 cells to the BM [Nat Commun] Full Article

Lung IFNAR1^hi TNFR2⁺ cDC2 Promotes Lung Regulatory T Cells Induction and Maintains Lung Mucosal Tolerance at Steady State

Researchers identified a lung IFNAR1^hiTNFR2⁺ conventional DC2 (iR2D2) population that induced T-regs in the lung at steady state. Using conditional knockout mice, adoptive cell transfer, receptor blocking antibodies, and TNFR2 agonists, they showed that iR2D2 was a lung microenvironment-adapted dendritic cell population whose residence depended on the constitutive TNFR2 signaling. [Mucosal Immunol] Full Article

Blockade of IL-6 Signaling Prevents Paclitaxel-Induced Neuropathy in C57Bl/6 Mice

The authors investigated whether intracellular calcium signaling and activation of calcium dependent proteases processes were linked by the pro-inflammatory cytokine IL-6. They observed that paclitaxel exposure induced IL-6 synthesis in cultured sensory neurons from postnatal Wistar rats, which could be prevented by co-treatment with a calpain inhibitor. [Cell Death Dis] Full Article

Effects of Thrombospondin-4 on Pro-Inflammatory Phenotype Differentiation and Apoptosis in Macrophages

Researchers examined the effects of A387-thrombospondin (TSP)-4 and P387-TSP-4 on mouse macrophages in cell culture and in vivo in the model of LPS-induced peritonitis. In tissues and in cell culture, TSP-4 expression was associated with inflammation: TSP-4 expression was upregulated in peritoneal tissues in LPS-induced peritonitis, and pro-inflammatory signals, INFγ, GM-CSF, and LPS, induced TSP-4 expression in macrophages in vivo and in cell culture. [Cell Death Dis] Full Article

Role of Interleukin-23 in the Development of Nonallergic Eosinophilic Inflammation in a Murine Model of Asthma

The authors developed a murine model of nonallergic eosinophilic asthma (NAEA) using recombinant IL-23 plus a nonspecific airway irritant or diesel exhaust particles (DEPs) and investigated whether IL-23 played an important role in the development of NAEA. Intranasal administration of rIL-23plus polyinosinic-polycytidylic acid or DEPs without allergen resulted in methacholine bronchial hyperresponsiveness and eosinophilic airway inflammation in mice, which were characteristic features of NAEA. [Exp Mol Med] Full Article

Deciphering the Crosstalk Between Myeloid-Derived Suppressor Cells and Regulatory T Cells in Pancreatic Ductal Adenocarcinoma

By using light sheet fluorescent microscopy, investigators identified direct interactions between these major immunoregulatory cells in pancreatic ductal adenocarcinoma. The in vivo depletion of myeloid-derived suppressor cells led to a significant reduction in Tregs in the pancreatic tumors. [Front Immunol] Abstract

TAK-242 Ameliorates Contact Dermatitis Exacerbated by IL-36 Receptor Antagonist Deficiency

Investigators examined whether a loss-of-function interleukin-36 receptor antagonist (IL36RN) mutation exacerbates contact dermatitis and evaluated the changes in contact dermatitis-related cytokines. Wild-type and Il36rn^-/- mice were treated with 1-fluoro-2,4-dinitorobenzene and evaluated for ear thickness, histopathological features, numbers of infiltrated neutrophils, and numbers of CD4⁺ and CD8⁺-T cells. [Sci Rep] Full Article

The In Vivo Effect of Lacto-N-Neotetraose (LNnT) on the Expression of Type 2 Immune Response Involved Genes in the Wound Healing Process

Scientists evaluated the cell viability of fibroblasts in the presence of LNnT. The full-thickness wound model was created by punch biopsy. The mice were treated intradermaly with LNnT at the concentrations of 100 and 200 µg or PBS as a control group. [Sci Rep] Full Article

Subscribe to our sister publications: Human Immunology News & Immunology of Infectious Disease News.

Local Heroes or Villains: Tissue-Resident Memory T Cells in Human Health and Disease

The authors review the beneficial effects of tissue-resident memory T (T_RM) cells in mediating protective responses against infection and cancer and the adverse role of T_RM cells in driving pathology in autoimmunity. A further understanding of the breadth and mechanisms of T_RM cell activity is essential for the safe design of strategies that manipulate T_RM cells, such that protective responses can be enhanced without unwanted tissue damage, and pathogenic T_RM cells can be eliminated without losing local immunity. [Cell Mol Immunol] Abstract

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

Aldeyra Therapeutics Announces First Patient Enrolled in the Phase III INVIGORATE Trial in Allergic Conjunctivitis

Aldeyra Therapeutics, Inc. announced enrollment of the first patient into the Phase III INVIGORATE trial of topical ocular reproxalap in patients with allergic conjunctivitis. [Aldeyra Therapeutics, Inc.] Press Release

OSE Immunotherapeutics Announces Issuance of a New Patent in Japan for Tedopi^® on Inducing Early T-Lymphocyte Memory Response

OSE Immunotherapeutics announced that the Japanese Patent Office has issued a new patent family related to Tedopi^®, a combination of neoepitopes, protecting the product’s method for inducing early T-lymphocyte memory response for use in the treatment of cancer in HLA-A2 positive patients. [OSE Immunotherapeutics] Press Release

Anokion Announces FDA Clearance of IND Application for Its Lead Program in Celiac Disease

Anokion SA announced that the FDA has accepted its Investigational New Drug (IND) application for KAN-101, the company’s lead antigen-specific drug candidate. Anokion plans to initiate its multi-center Phase I study for KAN-101 in people with celiac disease in the first quarter of 2020. [Anokion SA] Press Release

‘We Need a People’s Cryo-EM’ Scientists Hope to Bring Revolutionary Microscope to the Masses

X-ray crystallography has dominated structural biology ever since, but it has an Achilles’ heel: Some proteins just can’t be coaxed to form crystals, which scatter X-rays to reveal structure. Cryo-electron microscopy dodges the problem of crystallization with a flash-freezing process that fixes proteins in thin films of glassy ice. [ScienceInsider] Editorial

Campus Attacks by Nationalists and Police Alarm India’s Scientific Community

The attack on one of India’s most prestigious universities sent shock waves around the country and is the latest sign that the political forces tearing apart Indian society are also affecting the country’s academic community. Students at JNU, a liberal bastion, had been on strike for months against both a major hike in student fees and the government’s controversial Citizenship Amendment Act, widely decried as discriminatory against Muslims. [ScienceInsider] Editorial

NEW 27^th International Molecular Medicine Tri-Conference
March 1-4, 2020
San Francisco, California, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Researcher – Immunoregulation (GlaxoSmithKline plc.)

Research Associate – Human Immunology (STEMCELL Technologies Inc.)

Scientist – Immunology (STEMCELL Technologies Inc.)

Postdoctoral Researcher – Immuno-Oncology (Essen University Hospital)

Postdoctoral Scientist – Granuloma (Texas Biomedical Research Institute)

Postdoctoral Position – Computational Single-Cell Biology (Max Planck Institute of Immunobiology and Epigenetics)

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)

Postdoctoral Scholar Position – Molecular Biology, Immunology and Synthetic Biology (University of California, Irvine)

Postdoctoral Fellow Positions – Computational Immunology/Biology (Memorial Sloan Kettering Cancer Center)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Immune Regulation News? Click here to submit!

Comments or suggestions? Submit your feedback here.