Immune Regulation News Volume 9.16 | May 5 2017

TOP STORY

Mayo Clinic Researchers Develop New Tumor-Shrinking Nanoparticle to Fight Cancer, Prevent Recurrence

A Mayo Clinic research team has developed a new type of cancer-fighting nanoparticle aimed at shrinking breast cancer tumors, while also preventing recurrence of the disease. Mice that received an injection with the nanoparticle showed a 70 to 80 percent reduction in tumor size. Mice treated with these nanoparticles showed resistance to future tumor recurrence, even when exposed to cancer cells a month later. [Press release from the Mayo Clinic discussing online prepublication in Nature Nanotechnology] Press Release | Abstract

(Ranked by impact factor of the journal)

Anti-Inflammatory Effect of IL-10 Mediated by Metabolic Reprogramming of Macrophages

Scientists showed that interleukin 10 (IL-10) opposes the switch to the metabolic program induced by inflammatory stimuli in macrophages. Specifically, they showed that IL-10 inhibits lipopolysaccharide-induced glucose uptake and glycolysis and promotes oxidative phosphorylation. IL-10 suppresses mammalian target of rapamycin (mTOR) activity through the induction of an mTOR inhibitor, DDIT4. [Science] Abstract

Cholesterol Accumulation in Dendritic Cells Links the Inflammasome to Acquired Immunity

The significance of impaired cholesterol efflux pathways in autoimmunity is unknown. Researchers observed that ATP binding cassette transporters A1 and G1 (Abca1/g1)-deficient mice develop enlarged lymph nodes (LNs) and glomerulonephritis suggestive of systemic lupus erythematosus. This lupus-like phenotype was recapitulated in mice with knockouts of Abca1/g1 in dendritic cells (DCs), but not in macrophages or T cells. DC-Abca1/g1 deficiency increased LN and splenic CD11b⁺ DCs, which displayed cholesterol accumulation and inflammasome activation, increased cell surface levels of the granulocyte macrophage-colony stimulating factor receptor, and enhanced inflammatory cytokine secretion. [Cell Metab] Abstract | Graphical Abstract

Brd4 Modulates the Innate Immune Response through Mnk2–eIF4E Pathway-Dependent Translational Control of IκBα

The authors demonstrated that mice deficient for Brd4 in myeloid-lineage cells are resistant to LPS-induced sepsis but are more susceptible to bacterial infection. Gene-expression microarray analysis of bone marrow-derived macrophages revealed that deletion of Brd4 decreases the expression of a significant amount of LPS-induced inflammatory genes while reversing the expression of a small subset of LPS-suppressed genes, including MAP kinase-interacting serine/threonine-protein kinase 2 (Mknk2). [Proc Natl Acad Sci USA] Abstract | Press Release

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Researchers defined an antigen-independent, contact-dependent, adhesive guidance system for follicular T helper (T_FH) cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecules, which are highly expressed by germinal center (GC) B cells, and their transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on T_FH cells. Sema4C on T_FH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases T_FH migration inwards at the GC edge to promote GC access. [Cell Rep] Full Article | Graphical Abstract

A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells

By combining index sorting of single embryonic hemogenic precursors with in vitro hematopoietic stem cells (HSC) maturation and transplantation assays, investigators analyzed emerging HSC precursor (pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. RClonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes. [Stem Cell Reports] Full Article

Combining DNA Vaccine and AIDA-1 in Attenuated Salmonella Activates Tumor-Specific CD4⁺ and CD8⁺ T-Cell Responses

The authors designed a vaccine vector containing the AIDA-1 autotransporter and DNA vaccine elements, generating a murine melanoma vaccine that was delivered by the attenuated Salmonella strain SL7207. Growth of murine subcutaneous melanoma was significantly inhibited by intranasal immunization with the Salmonella tumor vaccine. The vaccine activated tumor-specific CD4⁺ and CD8⁺ T-cell responses, with increased T cell proliferation, tumor antigen-specific Th1 cytokine production, increased percentages of tetramer positive cells, and cytotoxicity. [Cancer Immunol Res] Abstract

Egr2 and 3 Inhibit T-Bet–Mediated IFN-γ Production in T Cells

Researchers discovered that Egr2 and 3 are potent inhibitors of T-bet function in CD4 and CD8 effector T cells. Egr2 and 3 were essential to suppress Th1 differentiation in Th2 and Th17 conditions in vitro and also to control IFN-γ–producing CD4 and CD8 T cells in response to virus infection. Together with Egr2 and 3, T-bet was induced in naive T cells by Ag stimulation, but Egr2 and 3 expression was inhibited by Th1–inducing cytokines. They found that Egr2 and 3 physically interact with the T-box domain of T-bet, blocking T-bet DNA binding and inhibiting T-bet–mediated production of IFN-γ. [J Immunol] Full Article

Protein Kinase CK2 Controls the Fate between Th17 Cell and Regulatory T Cell Differentiation

Scientists demonstrated that CK2 expression and kinase activity are induced upon CD4⁺ T cell activation. Targeting the catalytic activity of CK2 using the next-generation small molecule inhibitor CX-4945 in vitro significantly and specifically inhibited mouse and human Th17 cell differentiation while promoting the generation of Foxp3⁺ regulatory T cells. [J Immunol] Abstract

T-Cell Activation RhoGTPase-Activating Protein Plays an Important Role in T_H17-Cell Differentiation

Investigators hypothesized that T-cell activation RhoGTPase-activating protein (TAGAP) plays key roles in the differentiation and/or function of T_H17 cells. To evaluate this hypothesis, they analyzed the effect of TAGAP on T_H17 differentiation in vitro and established a line of TAGAP-deficient mice. They found that TAGAP was required for T_H17 differentiation in vitro and that the loss of TAGAP in mice ameliorated the clinical features of experimental autoimmune encephalomyelitis, indicating that TAGAP is critical for disease progression. [‎Immunol Cell Biol] Abstract

Platelets Subvert T Cell Immunity against Cancer via GARP-TGFβ Axis

The authors hypothesized that platelets promote malignancy and resistance to therapy by dampening host immunity. They showed that genetic targeting of platelets enhances adoptive T cell therapy of cancer. An unbiased biochemical and structural biology approach established transforming growth factor β (TGFβ) and lactate as major platelet-derived soluble factors to obliterate CD4⁺ and CD8⁺ T cell functions. [Sci Immunol] Abstract

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

Metabolic Instruction of Immunity

This review of immunometabolism references the most recent literature to cover the choices that environments impose on the metabolism and function of immune cells and highlight their consequences during homeostasis and disease. [Cell] Full Article | Graphical Abstract

Role of MicroRNAs in the Development and Function of Innate Immune Cells

The authors review how several microRNAs have shown to be activated during the inflammatory response and they limit the excessive immune response. The dysregulation of several microRNAs have shown to cause uncontrolled production of inflammatory cytokines resulting in various diseases. MicroRNAs are found to be crucial regulators of the development and function of innate immune cells and maintenance of immune homeostasis. [Int Rev Immunol] Abstract

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

White Blood Cell Count Predicts Response to Lung Cancer Immunotherapy

Researchers assessed the ability of white blood cell counts to predict whether lung cancer patients responded to treatment with nivolumab. [Press release from the European Society for Medical Oncology discussing research to be presented at the European Lung Cancer Conference (ELCC), Geneva] Press Release

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

French Plan to Create €5-Billion Science ‘Super-Campus’ in Disarray

French ambitions to create a €5-billion (US$5.5-billion) science ‘super-campus’ near Paris by 2020 seem to be in falling further apart, after a compromise scheme to save the troubled project was rejected by one of its creators. [Nature News] Editorial

NIH Grant Limits Rile Biomedical Research Community

A decision by the US National Institutes of Health (NIH) to limit its grant support for individual researchers has sparked concerns that the policy could discourage collaboration or divert funding from the best science. The move has alarmed some researchers who agree with the NIH’s stated aim of freeing up money for young scientists, who often struggle to obtain research grants. [Nature News] Editorial

NEW Keystone Symposium: Aging & Mechanisms of Aging-Related Disease
May 15-19, 2017
Yokohama, Japan

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

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

NEW Scientist – Analytical Development (KBI Biopharma)

NEW Postdoctoral Research Fellow – Immunotherapy (Fred Hutchinson Cancer Research Center)

Research Associate – Innate Immune Responses (University of Glasgow)

Senior Scientist – Molecular and Cellular Neuroimmunology (Pfizer)

Postdoctoral Fellow – Anderson Faculty (Wellcome Trust Sanger Institute)

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

Senior Research Scientist – Natural Killer Cell Therapy (Anthony Nolan)

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

Postdoctoral Positions – Computational Biology (The University of Texas MD Anderson Cancer Center)

Principal Scientist – Immuno Oncology (Celgene Corporation)

Assistant Associate or Full Member – 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 Immune Regulation News? Click here to submit!

Comments or suggestions? Submit your feedback here.