Immune Regulation News Volume 12.18 | May 22 2020

TOP STORY

Type 1 T_reg Cells Promote the Generation of CD8⁺ Tissue-Resident Memory T Cells

Investigators showed that type 1 regulatory T (Treg) cells, which express the transcription factor T-bet, promoted the generation of CD8⁺ tissue resident memory (TRM) cells. The absence of T-bet-expressing type 1 T_reg cells reduced the presence of TRM cells in multiple tissues and increased pathogen burden upon infectious challenge. [Nat Immunol] Abstract

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Adoptive Cellular Therapy with T Cells Expressing the Dendritic Cell Growth Factor Flt3L Drives Epitope Spreading and Antitumor Immunity

Researchers engineered T cells to secrete the dendritic cell (DC) growth factor Fms-like tyrosine kinase 3 ligand (Flt3L). Flt3L-secreting T cells expanded intratumoral conventional type 1 DCs and substantially increased host DC and T cell activation when combined with immune agonists poly and anti-4-1BB. [Nat Immunol] Abstract

Caspase-8-Dependent Inflammatory Responses Are Controlled by Its Adaptor, FADD, and Necroptosis

Scientists describe oligomerization-deficient Caspase-8^{F122GL123G/F122GL123G} and non-cleavable Caspase-8^D387A/D387A mutant mice with defective caspase-8-mediated apoptosis. Although neither mouse developed lymphoproliferative disease, removal of the necroptosis effector Mlkl from Caspase-8^D387A/D387A mice revealed an inflammatory role of caspase-8. [Immunity] Abstract | Graphical Abstract

Single-Cell RNA Sequencing to Dissect the Immunological Network of Autoimmune Myocarditis

Mice were treated with myosin heavy-chain-α peptides to generate an experimental autoimmune myocarditis (EAM) model. The authors performed single-cell RNA sequencing analysis of Cd45⁺ cells extracted from mouse hearts during different EAM phases, including normal control, acute inflammatory, subacute inflammatory and myopathy phases. [Circulation] Abstract

S100A9 Links Inflammation and Repair in Myocardial Infarction

Scientists assessed cardiac function, hematopoietic response, and myeloid phagocyte dynamics in wild-type C57BL/6 mice with permanent coronary artery ligation, treated with the specific S100A9 blocker ABR-238901 for seven or 21 days. [Circ Res] Abstract

Dynamic Transcriptome Analysis Unveils Key Pro-Resolving Factors of Chronic Inflammatory Arthritis

Adenovirus-mediated transfer of the Ywhaz gene to the affected joints substantially inhibited arthritis progression in mice with collagen-induced arthritis and suppressed expression of pro-inflammatory cytokines in joint tissues, lymph nodes, and spleens, suggesting Ywhaz as an excellent target for rheumatoid arthritis therapy. [J Clin Invest] Abstract | Full Article | Graphical Abstract

Peripheral Nerve Resident Macrophages Share Tissue-Specific Programming and Features of Activated Microglia

By comparing gene expression across neural and conventional tissue-resident macrophages, researchers identified transcripts that were shared among neural resident macrophages as well as selectively enriched in peripheral nervous system macrophages. [Nat Commun] Full Article

Glycopeptide Epitope Facilitates HIV-1 Envelope Specific Humoral Immune Responses by Eliciting T Cell Help

Scientists report that a CD4⁺ T cell repertoire recognized a glycopeptide epitope on gp120 presented by MHCII pathway. This glycopeptide was strongly immunogenic in eliciting glycan-dependent cellular and humoral immune responses. [Nat Commun] Full Article

Low-Frequency Ultrasound-Mediated Cytokine Transfection Enhances T Cell Recruitment at Local and Distant Tumor Sites

The authors developed a flexible protocol to efficiently transfect tumor and stromal cells to produce immune-activating cytokines, and thus enhanced T cell infiltration while debulking tumor mass. By combining ultrasound with tumor-targeted microbubbles, membrane pores were created and facilitated a controllable and local transfection. [Proc Natl Acad Sci USA] Abstract

Marginal Zone SIGN-R1⁺ Macrophages Are Essential for the Maturation of Germinal Center B Cells in the Spleen

Investigators found that while SIGN-R1⁺ macrophages were not essential for initial activation of B cells, they were required for maturation of the response and development of germinal center B cells. [Proc Natl Acad Sci USA] Full Article

CD8⁺ T-Cell-Mediated Immunoediting Influences Genomic Evolution and Immune Evasion in Murine Gliomas

Researchers developed retrovirus-induced PDGF⁺Pten^-/- murine gliomas and evaluated glioma progression and tumor immunogenicity in the absence of CD8⁺ T-cells by depleting this immune cell population. [Clin Cancer Res] Abstract

Characterization of Tumor-Infiltrating Lymphocytes in a Tumor Rejection Cynomolgus Macaque Model

Scientists characterized tumor-infiltrating lymphocytes (TILs) in a cynomolgus macaque tumor model in which the tumors were infiltrated with CD4⁺ and CD8⁺ T cells and were eventually rejected. [Sci Rep] Full Article

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The CD47-SIRPα Immune Checkpoint

The authors review the current understanding of the role of the CD47-SIRPα axis in physiological tissue homeostasis and as a promising therapeutic target in, among others, oncology, fibrotic diseases, atherosclerosis, and stem cell therapies. [Immunity] Abstract

Antigen Presentation by Dendritic Cells and Their Instruction of CD4⁺ T Helper Cell Responses

Investigators review current information on dendritic cell biology, their heterogeneity, and the properties of different dendritic cell subsets. [Cell Mol Immunol] Abstract

Recent Insights of T Cell Receptor-Mediated Signaling Pathways for T Cell Activation and Development

Scientists summarize current knowledge on the pathways that govern how the T cell receptor complex transmits signals into cells and the roles of effector molecules that are involved in these pathways. [Exp Mol Med] Abstract

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

Alethia Biotherapeutics Announces Receipt of FDA Authorization to Begin Phase II Development for Its EMT Inhibitor, AB-16B5

Alethia Biotherapeutics announced that the FDA has cleared its Phase II Investigational new drug application for AB-16B5, a potent inhibitor of the epithelial to mesenchymal transition (EMT). [Alethia Biotherapeutics] Press Release

FDA Approves Roche’s Tecentriq as a First-Line Monotherapy for Certain People with Metastatic Non-Small Cell Lung Cancer

Roche announced that the FDA has approved Tecentriq^® as a first-line treatment for adults with metastatic non-small cell lung cancer whose tumors have high PD-L1 expression or PD-L1 stained tumor-infiltrating [IC] covering ≥ 10% of the tumor area, as determined by an FDA-approved test, with no EGFR or ALK genomic tumour aberrations. [Roche] Press Release

Will Trump White House Tear Down Journal Paywalls? Many Anxiously Await a Decision

Scientific publishers, universities, librarians, and open-access advocates are waiting anxiously to see whether the Trump administration will end a long-standing policy and require that every scholarly article produced with US funding be made immediately free to all. [ScienceInsider] Editorial

Are Women Publishing Less during the Pandemic? Here’s What the Data Say

Early analyses suggest that female academics are posting fewer preprints and starting fewer research projects than their male peers. [Nature News] Editorial

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NEW Postdoctoral Associate – G Protein-Coupled Receptors (Howard Hughes Medical Institute)

Postdoctoral Fellow – Mechanisms of Autoimmune Disease (Oklahoma Medical Research Foundation)

PhD Studentship – Antibody Diversity (University of Southern Denmark)

Postdoctoral Fellowships – Autoimmune Conditions (Benaroya Research Institute at Virginia Mason)

Postdoctoral Associate – Immunology and Mitochondrial Biology (Texas A&M Health Science Center)

Principle Scientist – Immunology and Gene Engineering (Empyrean Therapeutics Ltd)

Postdoctoral Researcher – Immune Checkpoint Therapy (Canadian Nuclear Laboratories)

Chair – Department of Microbiology and Immunology (Western University)

Postdoctoral Fellow – Acute Myeloid Leukemia (Icahn School of Medicine at Mount Sinai)

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

Principle Scientist – Cancer and Auto-Immune Disorders (Sanofi)

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