Immune Regulation News Volume 5.20 | May 31 2013

Neutrophil Swarms Require LTB4 and Integrins at Sites of Cell Death In Vivo
Using two-photon intravital microscopy in mouse models of sterile injury and infection, scientists showed a critical role for intercellular signal relay among neutrophils mediated by the lipid leukotriene B4 (LTB4), which acutely amplifies local cell death signals to enhance the radius of highly directed interstitial neutrophil recruitment. [Nature] Abstract | Press Release

Malt1-Induced Cleavage of Regnase-1 in CD4⁺ Helper T Cells Regulates Immune Activation
Investigators showed that Regnase-1 is essential for preventing aberrant effector CD4⁺ T cell generation cell autonomously. Moreover, in T cells, Regnase-1 regulates the mRNAs of a set of genes, including c-Rel, Ox40, and Il2, through cleavage of their 3′ UTRs. [Cell] Abstract | Graphical Abstract | Press Release

GATA-3 Controls the Maintenance and Proliferation of T Cells Downstream of TCR and Cytokine Signaling
Scientists found that signaling via the T cell antigen receptor (TCR) and cytokine stimulation promoted GATA-3 expression in CD8⁺ T cells, which controlled cell proliferation. Although GATA-3-deficient CD8⁺ T cells were generated, their peripheral maintenance was impaired, with lower expression of the receptor for interleukin 7. [Nat Immunol] Abstract | Press Release

MARCH1-Mediated MHCII Ubiquitination Promotes Dendritic Cell Selection of Natural Regulatory T Cells
Researchers showed that membrane-associated RING-CH1 (MARCH1) deficiency resulted in a substantial reduction in the number of thymus-derived regulatory T cells (T reg cells) in mice. A specific ablation of MHCII ubiquitination also significantly reduced the number of thymic T reg cells. [J Exp Med] Abstract

Innate Pro-B-Cell Progenitors Protect against Type 1 Diabetes by Regulating Autoimmune Effector T Cells
Innate immune stimuli confer regulatory functions to various mature B-cell subsets but immature B-cell progenitors endowed with suppressive properties per se or after differentiating into more mature regulatory B cells remain to be characterized. The authors provide evidence for innate pro-B cells that emerged within the bone marrow both in vitro and in vivo upon Toll-like receptor-9 activation and whose adoptive transfer protected nonobese diabetic mice against type 1 diabetes. [Proc Natl Acad Sci USA] Abstract

Aire-Expressing Thymic Medullary Epithelial Cells Originate from β5t-Expressing Progenitor Cells
Investigators report the preparation and characterization of mice that express the recombinase Cre instead of β5t, a proteasome subunit that is abundant in cortical thymic epithelial cells (TECs) and not detected in other cell types, including medullary TECs. By crossing β5t-Cre knock-in mice with loxP-dependent GFP reporter mice, they found that β5t-Cre-mediated recombination occurs specifically in TECs but not in any other cell types in the mouse. [Proc Natl Acad Sci USA] Abstract | Press Release

Recovery from Overt Type 1 Diabetes Ensues When Immune Tolerance and β Cell Formation Are Coupled with Regeneration of Endothelial Cells in the Pancreatic Islets
The authors previously showed that Ig-GAD2, carrying glutamic acid decarboxylase (GAD) 206-220 peptide, induced in hyperglycemic mice immune modulation that was able to control pancreatic inflammation, stimulate β-cell regeneration and prevent type 1 diabetes (T1D) progression. Herein, they showed that the same Ig-GAD2 regimen given to mice with overt T1D is unable to reverse the course of disease despite eradication of Th1 and Th17 cells from the pancreas. [Diabetes] Abstract | Press Release

Sam68 Modulates the Promoter Specificity of NF-κB and Mediates Expression of CD25 in Activated T Cells
Results demonstrated that Src-associated substrate during mitosis of 68 kDa (Sam68) has an essential role in the induction and maintenance of CD25 in T cells. T-cell receptor engagement triggers translocation of the inhibitor of nuclear factor-kappaB (NF-κB) kinase alpha from the cytoplasm to the nucleus, where it phosphorylates Sam68, causing complex formation with NF-κB in the nucleus. [Nat Commun] Abstract

Loss of TLR2 Worsens Spontaneous Colitis in MDR1A Deficiency through Commensally Induced Pyroptosis
The authors investigated the role of TLR/IL-1R signaling pathways including the common adaptor MyD88 in the pathogenesis of chronic colonic inflammation in MDR1A deficiency. [J Immunol] Full Article

Antitumor Activity of IL-32β through the Activation of Lymphocytes, and the Inactivation of Nuclear Factor KappaB and Signal Transducer and Activator of Transcription 3 Signals
Researchers investigated whether interleukin (IL)-32β overexpression changes other cytokine levels and activates cytotoxic lymphocytes, and thus modifies tumor growth. [Cell Death Dis] Full Article

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Activation and Regulation of the Inflammasomes
The authors discuss the complex regulatory mechanisms that facilitate a balanced but effective inflammasome-mediated immune response, and they highlight the similarities to another molecular signaling platform – the apoptosome – that monitors cellular health. Extracellular regulatory mechanisms are discussed, as well as the intracellular control of inflammasome assembly, for example, via ion fluxes, free radicals and autophagy. [Nat Rev Immunol] Abstract

Friendly Pathogens: Prevent or Provoke Autoimmunity
Investigators highlight the interaction between different gut microbes and cells of immune system and the mechanism involved in controlling and curtailing various autoimmune diseases. [Crit Rev Microbiol] Abstract

B-Regulatory Cells in Autoimmunity and Immune Mediated Inflammation
B cells are a source of inhibitory cytokines such as IL-10 and TGF-β. The ability of being B-regulatory cells (B-regs) was shown to be driven by many stimulatory factors such as toll-like receptors, CD40-ligand and others. However, the characterization of B-regs is still underway. B-regs express high levels of CD25, CD86, IL-10 and TGF-β. In addition, the authors propose that semaphorin3A is a regulatory molecule and therefore can serve as one of the additional markers for B-regs. [FEBS Lett] Abstract

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

Prometheus Laboratories Launches PROCLIVITY 02, a Phase IV Multi-Center Study Comparing the Sequence of Proleukin® (Aldesleukin for Injection) and Yervoy® (Ipilimumab) in Patients with Metastatic Melanoma
Prometheus Laboratories Inc. announced that PROCLIVITY02, a multi-center study comparing the sequence of Proleukin® (High Dose Interleukin-2) followed by ipilimumab to the converse order, as therapy in patients with metastatic melanoma has Investigational Review Board approval and anticipates enrolling patients this summer. [Prometheus Laboratories Inc.] Press Release

XBiotech Announces Development of a Novel True Human™ Antibody Therapeutic
XBiotech announced its development of a novel True Human™ therapeutic antibody. The Company reports that the antibody neutralizes a pro-inflammatory molecule known as interleukin-6. The Company is now developing a manufacturing process for the antibody, and expects to be ready for clinical studies in early 2014. [XBiotech USA, Inc.] Press Release

CDRD and CDRD Ventures Inc. Enter into a Collaboration with GSK to Advance the Development and Commercialization of Canadian Health Research
The Centre for Drug Research and Development (CDRD), its commercial arm, CDRD Ventures Inc., and GlaxoSmithKline (GSK) in Canada announced they have entered into a strategic collaboration that will provide new financial resources as well as leading drug development expertise to be applied to the development and commercialization of health research conducted in Canadian research institutions. [GlaxoSmithKline Inc.] Press Release

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NEW 14th International Congress on Antiphospholipid Antibodies (APLA) & 4th Latin American Congress on Autoimmunity (LACA)
September 18-21, 2013
Rio de Janeiro, Brazil

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

NEW Junior or Senior Group Leader – Immunology/Infection/Inflammation (Center of Pathophysiology of Toulouse Purpan)

Research Associates – Immune Response (NCSR Demokritos, Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety)

Researcher – In Vivo Imaging of Disease Activity in Immune Mediated Diseases (Westfalische Wilhelms-Universitat Muenster)

Postdoctoral Position – Mechanistic Studies in Immune Responses (Medical University of Vienna)

Research Associate – NeuroOncology (University of Chicago – Department of Surgery)
 
PhD Studentship – Role of Epigenetic Regulators in Control of Immunity and Inflammation (King’s College London)

Postdoctoral Researcher – Innate Immunity (Massachusetts General Hospital / Harvard Medical School)

Postdoctoral Fellowship – Tumor Immunology (Northwestern University – Robert H Lurie Comprehensive Cancer Center)

Postdoctoral Fellow – Immunological Pathways in Human Inflammatory Bowel Disease (Yale University – School of Medicine)

Postdoctoral Position – Immunology (INSERM 1020)

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