Human Immunology News Volume 6.46 | Nov 20 2018

TOP STORY

Human Cell Atlas Study Reveals How the Maternal Immune System Is Modified Early in Pregnancy

The first Human Cell Atlas study of early pregnancy in humans has shown how the function of the maternal immune system is affected by cells from the developing placenta. Researchers used genomics and bioinformatics approaches to map over 70,000 single cells at the junction of the uterus and placenta. This revealed how the cells talk to each other to modify the immune response and enable the pregnancy. [Press release from the Wellcome Sanger Institute discussing online prepublication in Nature] Press Release | Abstract

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Genome-Wide CRISPR Screens in Primary Human T Cells Reveal Key Regulators of Immune Function

The authors developed a new method, single guide RNA lentiviral infection with Cas9 protein electroporation, to identify regulators of stimulation responses in primary human T cells. [Cell] Abstract | Graphical Abstract

Enhancing T Cell Receptor Stability in Rejuvenated iPSC-Derived T Cells Improves Their Use in Cancer Immunotherapy

Scientists report that CD8αβ T cells from human induced pluripotent stem cells (iPSCs) derived from antigen-specific T cells lose their antigen specificity through additional rearrangement of the T cell receptor α chain gene during the CD4/CD8 double positive stage of in vitro differentiation. [Cell Stem Cell] Abstract | Graphical Abstract

DEL-1 Promotes Macrophage Efferocytosis and Clearance of Inflammation

Investigators found that developmental endothelial locus-1 (DEL-1), a secreted protein that inhibits leukocyte-endothelial adhesion and inflammation initiation, also functions as a non-redundant downstream effector in inflammation clearance. [Nat Immunol] Abstract | Press Release

Cross-Reactive Dengue Virus Antibodies Augment Zika Virus Infection of Human Placental Macrophages

The authors found that dengue virus antibodies increase Zika virus infection of placental macrophages from 10% to over 80% and enhance infection of human placental explants. [Cell Host Microbe] Full Article | Graphical Abstract

Cellular Metabolism Constrains Innate Immune Responses in Early Human Ontogeny

Investigators showed transcriptomic, metabolic and polysome profiling and found that monocytes isolated from infants born early in gestation displayed perturbations in PPAR-γ-regulated metabolic pathways, limited glycolytic capacity and reduced ribosomal activity. [Nat Commun] Full Article

The CD4⁻CD8⁻ MAIT Cell Subpopulation Is a Functionally Distinct Subset Developmentally Related to the Main CD8⁺ MAIT Cell Pool

Scientists showed that the two mucosa-associated invariant T (MAIT) cell subsets express divergent transcriptional programs and distinct patterns of classic T cell transcription factors. Furthermore, CD8⁺ MAIT cells have higher levels of receptors for IL-12 and IL-18, as well as of the activating receptors CD2, CD9, and NKG2D, and display superior functionality following stimulation with riboflavin-autotrophic as well as riboflavin-auxotrophic bacterial strains. [Proc Natl Acad Sci USA] Full Article

Activation of miR-21-Regulated Pathways in Immune Aging Selects against Signatures Characteristic of Memory T Cells

Researchers showed that activation-induced upregulation of miR-21 biases the transcriptome of differentiating T cells away from memory T cells and toward inflammatory effector T cells. [Cell Rep] Full Article | Graphical Abstract

Prognostic and Therapeutic Significance of Phosphorylated STAT3 and Protein Tyrosine Phosphatase-6 in Peripheral-T Cell Lymphoma

Investigators analyzed phospho-STAT3 expression in a cohort of 169 peripheral T cell lymphoma (PTCL) tumors and showed overall 38% positivity with varied distribution among PTCL subtypes with 27% in PTCL-NOS; 29% in AITL, 57% in ALK-negative ALCL, and 93% in ALK-pos ALCL, respectively. [Blood Cancer J] Full Article

High-Affinity CD16-Polymorphism and Fc-Engineered Antibodies Enable Activity of CD16-Chimeric Antigen Receptor-Modified T Cells for Cancer Therapy

CD16-chimeric antigen receptor T cells were co-cultured with Panc-1 pancreatic cancer, Raji lymphoma or A375 melanoma cells in the presence or absence of anti-CD20, anti-MCSP, wild-type or the glycoengineered antibody variants. The endpoints were proliferation, activation, and cytotoxicity in vitro. [Br J Cancer] Abstract

Epstein-Barr Virus–Specific T Cell Therapy for Progressive Multiple Sclerosis

An open-label Phase I trial was designed to treat five patients with secondary progressive multiple sclerosis (MS) and five patients with primary progressive MS with four escalating doses of in vitro-expanded autologous EBV-specific T cells targeting EBV nuclear antigen 1, latent membrane protein 1 (LMP1), and LMP2A. [JCI Insight] Full Article | Press Release

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Human Natural Killer Cells and Other Innate Lymphoid Cells in Cancer: Friends or Foes?

Innate lymphoid cells (ILC) including NK cells and the recently identified “helper” ILC1, ILC2 and ILC3, play an important role in innate defenses against pathogens. Notably, they mirror analogous T cell subsets, regarding the pattern of cytokine produced, while the timing of their intervention is few hours vs days required for T cell-mediated adaptive responses. [Immunol Lett] Abstract

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BioInvent Signs Manufacturing Agreement with U.S. Cell Therapy Company

BioInvent International AB announced that it has signed a manufacturing agreement with an undisclosed U.S. cell therapy company for the production of cGMP compliant material to support their clinical development programs. [BioInvent International AB] Press Release

Cabaletta Bio Emerges Out of University of Pennsylvania to Develop CAAR T Cell Technology to Treat B Cell-Mediated Autoimmune Diseases

Cabaletta Bio Inc. has signed an exclusive license agreement and executed two multi-year sponsored research agreements with the University of Pennsylvania for the discovery and development of engineered T cell therapy products for B cell-mediated autoimmune disease. [Cabaletta Bio Inc. (Globe Newswire Inc.)] Press Release

Duke University to Settle Case Alleging Researchers Used Fraudulent Data to Win Millions in Grants

Duke University in Durham, North Carolina, is on the verge of settling a case brought by a former employee who claims the university included faked data in applications and reports for federal grants worth nearly $200 million. [ScienceInsider] Editorial

French Science Behemoth Launches Research-Integrity Office

France’s national research center, the CNRS, has announced plans to create its first office of research integrity to investigate scientific misconduct and promote good research practice. [Nature News] Editorial

In Reversal, NSF Lifts Proposal Limits on Biologists

In a reversal, the National Science Foundation (NSF) will no longer restrict researchers to only one proposal submission per year to the biology directorate’s three core tracks in which they are listed as a principal investigator (PI) or co-PI. [ScienceInsider] Editorial

NEW Keystone Symposia: B Cell-T Cell Interactions
February 10-14, 2019
Keystone, Colorado, United States

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