Human Immunology News Volume 5.17 | May 2 2017

TOP STORY

An Intermolecular FRET Sensor Detects the Dynamics of T Cell Receptor Clustering

Reseachers established a Förster resonance energy transfer (FRET) sensor, named CliF, which reports intermolecular associations of neighboring proteins in live cells. They found a correlation between cluster movement within the immunological synapse and cluster density. They developed a sensor that allows researchers to map the dynamics of protein clustering in live T cells. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Elevated Levels of Bcl-3 Inhibits Treg Development and Function Resulting in Spontaneous Colitis

Investigators revealed intrinsic functions of Bcl-3 in regulatory T (Treg) cells, identified Bcl-3 as a potential prognostic marker for colitis and illustrated the mechanism by which Bcl-3 regulates NF-κB activity in Tregs to prevent colitis. [Nat Commun] Full Article | Press Release

Proliferation of PD-1⁺ CD8 T Cells in Peripheral Blood after PD-1–Targeted Therapy in Lung Cancer Patients

Scientists analyzed longitudinal blood samples from advanced stage non–small cell lung cancer patients receiving programmed cell death 1 (PD-1)–targeted therapies. They detected an increase in Ki-67⁺ PD-1⁺ CD8 T cells following therapy in ~70% of patients, and most responses were induced after the first or second treatment cycle. This T cell activation was not indiscriminate because they observed only minimal effects on EBV-specific CD8 T cells, suggesting that responding cells may be tumor specific. [Proc Natl Acad Sci USA] Abstract | Press Release

Label-Free Analysis of CD8⁺ T Cell Subset Proteomes Supports a Progressive Differentiation Model of Human-Virus-Specific T Cells

To better understand the molecular mechanisms that drive functional specification, researchers used high-resolution mass spectrometry and label-free protein quantification to measure proteomic differences between the seven largest circulating human CD8⁺ T cell subsets. Hierarchical clustering of the proteomes placed naive and CD45RA-expressing effector-type T cells at the extremes of the spectrum, with central memory and other effector memory stages located in between. [Cell Rep] Full Article | Graphical Abstract

NFAT5-Sensitive Orai1 Expression and Store-Operated Ca²⁺ Entry in Megakaryocytes

The authors explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca²⁺-signaling in megakaryocytes. NFAT5 transfection or exposure to hypertonicity of megakaryocytic cells increased Orai1, Orai2, stromal interaction molecule (STIM)-1, and STIM2 transcript levels. Orai1 transcript levels were decreased by NFAT5 silencing. NFAT5 transfection and IκB inhibitor BMS 345541 increased, whereas NFAT5 silencing and SGK1 inhibitor GSK650394 decreased store-operated Ca²⁺-entry. [FASEB J] Abstract

IVIG Regulates the Survival of Human but Not Mouse Neutrophils

Investigators compared the effects of intravenous immunoglobulin (IVIG) on human and mouse neutrophils using different death assays. Different commercial IVIG preparations similarly induced cytokine-dependent death in human neutrophils, whereas they had no effects on the survival of either peripheral blood or bone marrow neutrophils from C57BL/6 or BALB/c mice. F(ab’)₂ but not Fc fragments of IVIG induced death of human neutrophils, whereas neither of these IVIG fragments, nor agonistic monoclonal antibodies to human Fas or Siglec-9 affected the viability of mouse neutrophils. [Sci Rep] Full Article

Transcriptional Landscape of Epithelial and Immune Cell Populations Revealed through FACS-Seq of Healthy Human Skin

To identify distinct transcriptomic profiles of multiple cell populations without substantially altering cell phenotypes, scientists employed a fluorescence activated cell sorting (FACS) method to isolate keratinocytes, dendritic cells, CD4⁺ T effector cells, and CD8⁺ T effector cells from healthy skin samples, followed by RNA-seq of each cell population. [Sci Rep] Full Article

CD40L-Dependent Pathway Is Active at Various Stages of Rheumatoid Arthritis Disease Progression

Researchers used gene signatures of CD40L stimulation derived from human immature dendritic cells and naïve B cells to assess the expression of CD40-downstream genes in synovial tissues from anti-citrullinated protein Ab–positive arthralgia, undifferentiated arthritis, early rheumatoid arthritis (RA), and established RA cohorts in comparison with healthy donors. The expression of CD40LG and active full-length CD40 was increased in the disease tissues, whereas that of a dominant-negative CD40 isoform was decreased. [J Immunol] Abstract

Phenotype, Function, and Differentiation Potential of Human Monocyte Subsets

Scientists phenotyped monocytes from peripheral blood of healthy subjects and performed functional studies on high-speed sorted subsets. Subset frequencies were found to be tightly controlled over time and across individuals. Subsets were distinct in their secretion of TNFα, IL-6, and IL-1β in response to TLR agonists, with classical monocytes being the most producers and non-classical monocytes the least. [PLoS One] Full Article

Aging Effects on T-Bet Expression in Human B Cell Subsets

In order to compare human and mouse B cell subset markers, the authors evaluated T-bet expression in human B cell subsets from individuals of different ages. They found T-bet expressed in unstimulated memory more than naïve B cells, and more in young individuals. TLR7 stimulation up-regulated T-bet in all B cell subsets from young and elderly individuals, and more in the elderly. [Cell Immunol] Abstract

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

BACH Transcription Factors in Innate and Adaptive Immunity

Scientists review recent studies which indicate widespread roles of BTB and CNC homology (BACH) proteins in controlling the development and function of the innate and adaptive immune systems, including the differentiation of effector and memory cells of the B and T cell lineages, CD4⁺ regulatory T cells and macrophages. [Nat Rev Immunol] Abstract

Reenergizing T Cell Anti-Tumor Immunity by Harnessing Immunometabolic Checkpoints and Machineries

The authors discuss how tumor cells evade immunosurveillance by modulating metabolic checkpoints in immune cells and discuss how memory T cells could provide effective anti-tumor responses by sustaining metabolic fitness and longevity. [Curr Opin Immunol] Abstract

Visit our reviews page to see a complete list of reviews in the human immunology research field.

TxCell and Inserm Collaborate to Develop New CAR-Tregs in Transplantation and Multiple Sclerosis

TxCell SA and Inserm Transfert, on behalf of Inserm and the Nantes University, announced the signature of a R&D collaboration agreement on the development of chimeric antigen receptor engineered CD8⁺Treg cells (CAR Tregs). [TxCell SA] Press Release

Concert Pharmaceuticals Initiates CTP-543 Phase II Trial in Alopecia Areata

Concert Pharmaceuticals, Inc. announced the initiation of a Phase IIa clinical trial evaluating CTP-543 for the treatment of moderate-to-severe alopecia areata, an autoimmune disorder in which the immune system attacks hair follicles, resulting in patchy or complete hair loss. CTP-543 is an orally-administered selective inhibitor of Janus kinases 1 and 2, known as JAK1 and JAK2, which are enzymes believed to be involved in this autoimmune disorder. [Concert Pharmaceuticals, Inc.] Press Release

Moderna Announces Positive Interim Phase I Clinical Data Demonstrating First mRNA Vaccine Candidate, mRNA-1440, Induces High Levels of Immunogenicity

Moderna Therapeutics announced positive interim data from an ongoing Phase I study of mRNA-1440, an mRNA infectious disease vaccine against avian H10N8 influenza, demonstrating mRNA-1440 induced high levels of immunogenicity, and was safe and well tolerated. [Moderna Therapeutics] Press Release

Altor BioScience Corporation Announces FDA Fast Track Designation for Lead Candidate ALT-803 in Patients with Non-Muscle Invasive Bladder Cancer

Altor BioScience Corporation announced that it has received Fast Track designation from the U.S. Food and Drug Administration (FDA) for its investigational interleukin-15 agonist complex, ALT-803, in combination with bacillus Calmette-Guérin, for the treatment of patients with non-muscle invasive bladder cancer. [Altor BioScience Corporation] Press Release

Researchers Frustrated by Italian Misconduct Probe

More than five years ago, Italian police began investigating allegations of research misconduct in papers by Alfredo Fusco, a prominent cancer scientist in Naples. Researchers frustrated by the case’s slow progress have told Nature that there is strong evidence that dozens of papers may contain manipulated data — and that a commercial photography studio was called in to cut and paste images. They say they are speaking out about the magnitude of the allegations because of their increasing impatience with the slow pace of investigations by police and by academic authorities. [Nature News] Editorial

How Science Fares in the U.S. Budget Deal

Congress has finally reached a deal on spending bills for the 2017 fiscal year. House of Representatives and Senate leaders announced that they expect lawmakers to vote this week on an agreement that wraps together all 12 appropriations bills that fund federal operations. For the past seven months, the government has been operating under a continuing resolution that froze 2017 spending at most agencies at 2016 levels and generally prevented them from starting new programs. [ScienceInsider] Editorial

NEW American Thoracic Society (ATS)
May 19-24, 2017
Washington, D.C., United States

NEW Cell Culture World Congress
May 23-24, 2017
San Diego, United States

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

NEW Tenure-Track Faculty Position(s) – Immunology (Cornell University)

NEW Postdoctoral Fellow – Rotavirus Vaccine Response (Wellcome Trust Sanger Institute)

Faculty Position – Cancer Immunology (Mayo Clinic)

Postdoctoral Fellow – Innate Immunity and Neurodegeneration (Mount Sinai Health System)

Postdoctoral Associate Position – Immunometabolism and Myeloid Cell Regulation within the Tumor Microenvironment (University of Louisville Health Science Center)

Postdoctoral Scholar – Multiple Sclerosis (University of Washington)

Postdoctoral Research Fellow – Inflammation and Immuno-Oncology (Yale School of Medicine)

Postdoctoral Fellow Position – Translational Immunology (The University of Utah)

Postdoctoral Fellow – Immune-Oncology (Johnson and Johnson)

Research Investigator – Immuno-Oncology (Bristol-Meyers Squibb)

Assistant Associate – Cancer Immunology (Fred Hutchinson Cancer Research 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 Human Immunology News? Click here to submit!

Comments or suggestions? Submit your feedback here.