Immune Regulation News Volume 9.29 | Aug 4 2017

TOP STORY

Analyses of a Mutant Foxp3 Allele Reveal BATF as a Critical Transcription Factor in the Differentiation and Accumulation of Tissue Regulatory T Cells

Scientists established mouse models harboring three unique missense Foxp3 mutations that were identified in patients with the autoimmune disease IPEX. The I363V and R397W mutations were loss-of-function mutations, causing multi-organ inflammation by globally compromising Treg cell physiology. By contrast, the A384T mutation induced a distinctive tissue-restricted inflammation by specifically impairing the ability of Treg cells to compete with pathogenic T cells in certain non-lymphoid tissues. [Immunity] Abstract | Graphical Abstract

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MLL4 Prepares the Enhancer Landscape for Foxp3 Induction via Chromatin Looping

Investigators found that MLL4 deficiency compromised the development of T_reg cells and resulted in a substantial decrease in monomethylated histone H3 Lys4 and chromatin interaction at putative gene enhancers, a considerable portion of which were not direct targets of MLL4 but were enhancers that interacted with MLL4-bound sites. [Nat Immunol] Abstract

Schistosome Egg Antigens, including the Glycoprotein IPSE/Alpha-1, Trigger the Development of Regulatory B Cells

Researchers investigated whether Schistosoma mansoni soluble egg antigens (SEAs) directly interact with B cells to enhance their regulatory potential, or act indirectly on B cells via SEA-modulated macrophage subsets. Both B cells as well as macrophages of the splenic marginal zone efficiently bound SEAs in vivo, but macrophages were dispensable for regulatory B cell induction as shown by macrophage depletion with clodronate liposomes. [PLoS Pathog] Full Article

B Cell Requirement for Robust Regulatory T Cell Responses to Friend Retrovirus Infection

The authors used the Friend virus (FV) model of retroviral infection in mice to investigate how viral infections induce Tregs. They showed that B cells provide essential signals for Treg expansion during FV infection. Treg responses were greatly diminished in B cell-deficient mice but could be restored by adoptive transfers of B cells at the time of infection. [MBio] Full Article

Regulatory T Cells with Superior Immunosuppressive Capacity Emigrate from the Inflamed Colon to Draining Lymph Nodes

Scientists utilized photoconvertible KikGR mice to track immune cells from the cecum and ascending colon in the steady state and DSS-induced colitis. They found that Tregs from the proximal colon migrated exclusively to the distal part of mesenteric lymph nodes in an S1PR1-dependent process. [Mucosal Immunol] Abstract

Thermoneutral Housing Temperature Regulates T-Regulatory Cell Function and Inhibits Ovabumin-Induced Asthma Development in Mice

Researchers treated asthmatic mice with standard temperature (ST, 20°C) or thermoneutral temperature (TT, 30°C). The results showed that the airway inflammatory cell counts in bronchoalveolar lavage fluid and airway hyperresponsiveness were significantly reduced in the mice treated with TT as compared with the mice treated with ST. The pulmonary Treg cells were increased in asthmatic mice after TT treatment. [Sci Rep] Full Article

Arsenic Exposure Impels CD4 Commitment in Thymus and Suppress T Cell Cytokine Secretion by Increasing Regulatory T Cells

The authors investigated the effect of arsenic exposure on thymocyte lineage commitment and the involvement of T_reg in arsenic-induced immunosuppression. Arsenic exposure promoted CD4 lineage commitment in a dose dependent manner supported by the expression of ThPOK in thymus. [Sci Rep] Full Article

Control of Regulatory T Cell Differentiation by the Transcription Factors Thpok and LRF

Investigators showed that Thpok and LRF are redundantly required to maintain the size and functions of the postthymic Treg pool. They support IL-2–mediated gene expression and the functions of the Treg-specific factor Foxp3. Treg-specific disruption of Thpok and Lrf caused a lethal inflammatory syndrome similar to that resulting from Treg deficiency. [J Immunol] Abstract

Quantitative and Qualitative Analysis of Regulatory T Cells in B Cell Chronic Lymphocytic Leukemia

Scientists demonstrated that chronic lymphocytic leukemia (CLL) derived CD4⁺CD25⁻CD127⁻ and CD4⁺CD25^lowCD127⁻ subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. They provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of T effector cells which in turn suppress CLL cells. [Leuk Res] Abstract

FICZ Generates Human tDCs that Induce CD4⁺ CD25^high Foxp3⁺ Treg-Like Cell Differentiation

The authors investigated the effect of 6-formylindolo(3,2-b)carbazole (FICZ), a natural aryl hydrocarbon receptor (AhR) ligand, on monocyte-derived dendritic cells (DCs) from healthy subjects. They found that the activation of AhR through FICZ during DC differentiation and maturation processes resulted in a decreased expression of CD83, an increased expression of the enzyme indoleamine 2,3-dioxygenase and a reduced production of the pro-inflammatory cytokines IL-6 and tumor necrosis factor alpha. [Immunol Lett] Abstract

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The Regulation of Immune Tolerance by FOXP3

Investigators summarize how the expression and activity of forkhead box protein P3 (FOXP3) are regulated across multiple layers by diverse factors. The therapeutic implications of these topics for cancer and autoimmunity are also discussed. [Nat Rev Immunol] Abstract

Mevalonate Metabolism Governs Cancer Immune Surveillance

The authors address how mevalonate metabolism drives immunity and highlight ways of the immune system to respond to both, limited and uncontrolled flux through the mevalonate pathway. [Oncoimmunology] Abstract | Full Article

Antigen-Specific Regulatory T-Cell Responses to Intestinal Microbiota

Researchers examine the mechanisms by which intestinal bacteria influence colonic T-cells and B-cell immunoglobulin A induction, with an emphasis on Treg cells and the role of antigen-specificity in these processes. In addition to discussing key primary literature, they highlight current controversies and important future directions. [Mucosal Immunol] Abstract

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Agragen Engineers Camelina to Produce a Biological Pharmaceutical for Treating Inflammatory Diseases to Dramatically Reduce the Costs for this Popular Drug

Agragen, LLC. announced a significant step in its development of its lead drug candidates, AGR131. Agragen’s unique production system will significantly reduce the production costs of AGR131, with an anticipated reduction in cost to patients of up to seventy-five percent compared to other drugs in this drug class. [Agragen, LLC.] Press Release

FDA Advisory Committee Does Not Recommend Approval of Sirukumab for the Treatment of Moderately to Severely Active Rheumatoid Arthritis

Janssen Biotech, Inc. announced that the Arthritis Advisory Committee of the U.S. FDA did not recommend approval of sirukumab for the treatment of moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or are intolerant to one or more disease modifying anti-rheumatic drugs. [Janssen Biotech, Inc.] Press Release

U.S. FDA Approves IMBRUVICA^® (Ibrutinib) as First and Only Approved Treatment for Adult Patients with Chronic Graft-versus-Host-Disease (cGvHD) after Failure of One or More Lines of Systemic Therapy

The U.S. FDA has approved IMBRUVICA^® for the treatment of adult patients with cGVHD after failure of one or more lines of systemic therapy. [Janssen Biotech, Inc.] Press Release

Protalex Completes Data Analysis of Second Dose Cohort of U.S. Phase I/II Study of PRTX-100 in ITP

Protalex, Inc. announced that following completion of a planned interim analysis of safety and efficacy data from the second dose cohort, the company is escalating the dose of PRTX-100 in its U.S. Phase I/II study of PRTX-100 in adults with persistent/chronic immune thrombocytopenia (ITP). [Protalex, Inc.] Press Release

TARGET PharmaSolutions Enrolls First Participant in its Inflammatory Bowel Disease (IBD) Community

TARGET PharmaSolutions, Inc. announced the enrollment of the first participant in its IBD community, TARGET-IBD, which includes adult and pediatric patients with ulcerative colitis, Crohn’s disease and indeterminate colitis. [TARGET PharmaSolutions, Inc.] Press Release

Chronic Diseases Spike in Middle East as Conflicts Rage

Across the Middle East, deaths resulting from violence grew by 850% between 1990 and 2015, according to a series of reports published on the 3^rd of August in the International Journal of Public Health. The increase accelerated after 2010, corresponding with the beginning of the Arab Spring movement and wars in Syria and Iraq. At the same time, the authors found, the incidence of many chronic diseases has also risen dramatically. [Nature News] Editorial

Drug Approval Needs a Helping Hand

It’s time for researchers to lend their expertise to expediting the arrival of cutting-edge therapies that are waiting in the wings. [Nature News] Editorial

Discredited Gene-Editing Researcher Vows to Clear His Name

A Chinese biologist whose team retracted a high-profile paper on a gene-editing technology has vowed to press ahead with experiments that he hopes will vindicate the potential rival to the CRISPR/Cas9 system. [ScienceInsider] Editorial

Iranian Scientist to Go on Trial for Espionage

An Iranian disaster-medicine researcher who was sent to prison in April 2016 is due to go to trial, on charges of “collaboration with a hostile government”. Ahmadreza Djalali has been warned by the Iranian court that he may be facing a death sentence, according to his wife, Vida Mehrannia. [Nature News] Editorial

NEW Multiple Sclerosis: Conventional and Alternative Therapeutic Approaches
August 15, 2017
Online, None

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NEW Postdoctoral Scolar – Tumor Immunology (Washington University School of Medicine)

NEW Postdoctoral Position – Mucosal Immunology (Sainte-Justine Hospital Research Center)

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Mouse Scientist – T Cell-Based Therapy (Tessa Therapeutics Pte Ltd.)

Postdoctoral Researcher – Tumor Immunology and Cancer Immunotherapy (University of California, Los Angeles)

Postdoctoral Fellow – Allergy and Immunology (New York University Medical Center)

Postdoctoral Fellow – Neuroimmunology (Duke University)

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

Principal Senior Scientist – Human Disease Immune Profiling/Precision Immunology (Sanofi)

Postdoctoral Fellow – Cell Biology and Innate Immunity (The Laboratory for Molecular Infection Medicine Sweden)

Postdoctoral Fellow – Inflammatory Bowel Disease (Harvard Medical School)

Assistant Associate or Full Member – Cancer Immunology (Fred Hutchinson Cancer Research Center)

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