Human Immunology News Volume 7.42 | Oct 29 2019

TOP STORY

MAIT Cells Are Imprinted by the Microbiota in Early Life and Promote Tissue Repair

Researchers demonstrated how early microbial encounters have long-term effects on the composition of the immune system. They showed that mucosal-associated invariant T (MAIT) cells were induced during a specific early-life window in response to riboflavin-synthesizing commensals. [Science] Abstract

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Broadly Protective Human Antibodies that Target the Active Site of Influenza Virus Neuraminidase

The authors describe three human monoclonal antibodies isolated from an H3N2-infected donor that bound with exceptional breadth to multiple different influenza A and B virus neuraminidases. These antibodies neutralized the virus, mediated effector functions, were broadly protective in vivo, and inhibited neuraminidase activity by directly binding to the active site. [Science] Abstract

Attacking Latent HIV with convertibleCAR-T Cells, a Highly Adaptable Killing Platform

Researchers designed a universal CAR-T cell platform based on cytotoxic T-lymphocytes (CTLs) engineered to bind a variety of broadly neutralizing anti-HIV antibodies. They showed that this platform, convertibleCAR-T cells, effectively killed HIV-infected, but not uninfected, CD4 T cells from blood, tonsil, or spleen and only when armed with anti-HIV antibodies. [Cell] Abstract | Press Release | Graphical Abstract

Transcriptional Basis of Mouse and Human Dendritic Cell Heterogeneity

By combining transcriptional and chromatin analyses with genetic reporter expression, investigators identified two principal cDC2 lineages defined by distinct developmental pathways and transcriptional regulators, including T-bet and RORγt, two key transcription factors known to define innate and adaptive lymphocyte subsets. [Cell] Full Article | Graphical Abstract

Proof-of-Concept Clinical Trial of Etokimab Shows a Key Role for IL-33 in Atopic Dermatitis Pathogenesis

Researchers noted significant reduction in skin neutrophil infiltration after etokimab compared with placebo upon skin challenge with house dust mite, reactivity to which has been implicated in the pathogenesis of atopic dermatitis. [Sci Transl Med] Abstract

Neutrophil Recruitment to Noninvasive MRSA at the Stratum Corneum of Human Skin Mediates Transient Colonization

Investigators demonstrated the importance of the outer stratum corneum as the major site of bacterial colonization and how noninvasive methicillin-resistant S. aureus (MRSA) adhesion to corneocytes induced a local inflammatory response in underlying skin layers. This signaling recruited neutrophils to the skin, where they controled bacterial numbers, mediating transiency in colonization. [Cell Rep] Full Article | Graphical Abstract

FOXP3 Protects Conventional Human T Cells from Premature Restimulation-Induced Cell Death

Scientists describe a novel role for forkhead box P3 (FOXP3) in protecting human conventional effector T cells (Tcons) from premature restimulation-induced cell death (RICD) during expansion. Unlike FOXP3-mediated protection from RICD in Tregs, FOXP3 protected Tcons through a distinct mechanism requiring de novo transcription that did not require SLAM-associated protein suppression. [Cell Mol Immunol] Abstract

Loss of Lkb1 Impairs Treg Function and Stability to Aggravate Graft-Versus-Host Disease after Bone Marrow Transplantation

Investigators demonstrated that regulatory T cells (Tregs) were more dramatically decreased in bone marrow compared with those in peripheral blood from acute graft-versus-host disease patients and that bone marrow Treg defects were negatively associated with hematopoietic reconstitution. [Cell Mol Immunol] Full Article

The Anti-Inflammatory Agent Bindarit Acts as a Modulator of Fatty Acid-Binding Protein 4 in Human Monocytic Cells

Scientists found that bindarit differentially regulated the release of interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), enhancing the release of IL-8 and reducing that of MCP-1. [Sci Rep] Full Article

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Role of Macrophage TRPV4 in Inflammation

The authors discuss the current understanding of the role of macrophage transient receptor potential channel subfamily V member 4 (TRPV4) in various inflammatory conditions. [Lab Invest] Abstract

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CARsgen Announces Investigational CAR-T Therapy CT053 Granted RMAT Designation by the US FDA for R/R Multiple Myeloma

CARsgen Therapeutics Co. Ltd. announced that the FDA has granted Regenerative Medicine Advanced Therapy (RMAT) designation to its investigational CT053 CAR-T cell therapy. [CARsgen Therapeutics Co. Ltd.] Press Release

Provention Bio Announces PRV-031 (Teplizumab) Granted PRIME Designation by the European Medicines Agency

Provention Bio, Inc. announced the European Medicines Agency has granted PRV-031 PRIority MEdicines (PRIME) designation for the prevention or delay of clinical type 1 diabetes in individuals at-risk of developing the disease. [Provention Bio, Inc.] Press Release

Arena Pharmaceuticals Announces First Subject Dosed in ADVISE Phase II Trial Evaluating Etrasimod in Atopic Dermatitis

Arena Pharmaceuticals, Inc. announced that the first subject has been dosed in the Phase II ADVISE trial evaluating etrasimod, an investigational next-generation, once-daily, oral, selective sphingosine 1-phosphate receptor modulator, for the potential treatment of moderate-to-severe atopic dermatitis. [Arena Pharmaceuticals, Inc.] Press Release

Academics in Ukraine Fighting against Rampant Misconduct

Plagiarism, pseudoscience, bribes, and cheating. The threats to academia in Ukraine are many, according to false-science, a group of around 10 Ukrainian scientists dedicated to battling cheaters. [The Scientist] Editorial

White House to Host Closed-Door Summit on US Research Enterprise

The White House Office of Science and Technology Policy will host a one-day meeting in Washington, DC, to discuss a host of hot-button issues affecting the US research community. [ScienceInsider] Editorial

Beware the UK Government’s Brexit Promises

There’s a research group in Britain that has become a staple of the country’s news shows, and it’s called The UK in a Changing Europe. On most nights, the team of political scientists, economists and lawyers dispassionately responds to broadcasters’ questions on the impact — economic, political and societal — of the United Kingdom’s departure from the European Union. [Nature News] Editorial

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