Immune Regulation News Volume 9.47 | Dec 8 2017

TOP STORY

Runx3 Programs CD8⁺ T Cell Residency in Non-Lymphoid Tissues and Tumors

The authors showed that mouse tissue-resident memory CD8⁺ T (T_RM) precursor cells represent a unique CD8⁺ T cell subset that is distinct from the precursors of circulating memory cell populations at the levels of gene expression and chromatin accessibility. Using computational and pooled in vivo RNA interference screens, they identified the transcription factor Runx3 as a key regulator of T_RM cell differentiation and homeostasis. [Nature] Abstract

(Ranked by impact factor of the journal)

Ablation of Transcription Factor IRF4 Promotes Transplant Acceptance by Driving Allogenic CD4⁺ T Cell Dysfunction

Scientists demonstrated that interferon regulatory factor 4 (IRF4) was a key transcriptional determinant controlling T cell responses during transplantation. IRF4 deletion in mice resulted in progressive establishment of CD4⁺ T cell dysfunction and long-term allograft survival. [Immunity] Abstract | Graphical Abstract

γδTCR Recruits the Syk/PI3K Axis to Drive Proinflammatory Differentiation Program

Researchers showed that the receptor proximal tyrosine kinase Syk is essential for γδ T cell receptor (TCR) signal transduction and development of IL-17–producing γδT (γδT17) in the mouse thymus. Zap70, another tyrosine kinase essential for the development of αβT cells, failed to functionally substitute for Syk in the development of γδT17. Syk induced the activation of the PI3K/Akt pathway upon γδTCR stimulation. [J Clin Invest] Full Article

Alternative Activation Generates IL-10 Producing Type 2 Innate Lymphoid Cells

Investigators showed induction of a molecularly distinct subset of activated lung type 2 innate lymphoid cells (ILC2), termed ILC210. These cells produced IL-10 and downregulated some pro-inflammatory genes. [Nat Commun] Full Article

Macrophage-Dependent Cytoplasmic Transfer during Melanoma Invasion In Vivo

To capture the cellular interactions of the tumor microenvironment with high-resolution imaging, researchers directly visualized tumor cells and their interactions with macrophages in zebrafish. The recruitment of macrophages to tumor cells promoted tumor cell dissemination. [Dev Cell] Full Article | Graphical Abstract

IL-33 and ST2 Mediate FAK-Dependent Antitumor Immune Evasion through Transcriptional Networks

Investigators identified a crucial, previously unknown role for the dual-function cytokine IL-33 in focal adhesion kinase (FAK)-dependent immune evasion. In murine squamous cell carcinoma cells, specifically nuclear FAK enhanced the expression of the genes encoding IL-33, the chemokine CCL5, and the soluble, secreted form of the IL-33 receptor, called soluble ST2. [Sci Signal] Full Article

TGFβ1 Transduction Enhances Immunomodulatory Capacity of Neural Stem Cells in Experimental Autoimmune Encephalomyelitis

Scientists engineered bone marrow-derived neural stem cells with inducible TGFβ1, a potent immunosuppressive cytokine, to enhance their anti-inflammatory capacity. Transduction of TGFβ1 resulted in a higher percentage of Tregs and lower percentage of Th1 and Th17 cells in the periphery, with increased production of IL-10, and reduced production of IFN-γ, IL-17 and GM-CSF. [Brain Behav Immun] Abstract

Regulatory B Cells Induced by Ultraviolet B through Toll-Like Receptor 4 Signaling Contribute to the Suppression of Contact Hypersensitivity Responses in Mice

Researchers investigated the inductive effect of ultraviolet (UV) B on regulatory B cells and the underlying mechanisms by using a contact hypersensitivity (CHS) mouse model. They found that UVB irradiation induced regulatory B cell expansion and ameliorated CHS. [Contact Dermatitis] Abstract

Sox2 Communicates with Tregs through CCL1 to Promote the Stemness Property of Breast Cancer Cells

Scientists disclose that the primarily cultured Tregs isolated from breast-tumor-bearing Foxp3-EGFP mouse upregulate the stemness property of breast cancer cells. [Stem Cells] Abstract

HIV-1-Associated Inflammation and Antiretroviral Therapy Regulate Astrocyte Endoplasmic Reticulum Stress Responses

The authors focused on unfolded protein responses and astrocyte elevated gene-1 regulation in primary human astrocytes exposed to HIV-associated neurocognitive disorders-relevant stimuli. IL-1β and the nucleoside reverse transcriptase inhibitor abacavir upregulated expression of endoplasmic reticulum stress markers in human astrocytes, including binding immunoglobulin protein, C/EBP homologous protein, and calnexin. [Cell Death Discov] Full Article

Migratory CD11b⁺ Conventional Dendritic Cells Induce T Follicular Helper Cell–Dependent Antibody Responses

Investigators used intranasal immunization as a physiologically relevant route of exposure that delivers antigen to all tissue dendritic cell (DC) subsets. Using a combination of mice in which the function of individual DC subsets is impaired and different antigen formulations, they determined that CD11b⁺ migratory type 2 conventional DCs are necessary and sufficient for T follicular helper induction. [Sci Immunol] Abstract | Press Release

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The Role of Semaphorins in Immune Responses and Autoimmune Rheumatic Diseases

The authors discuss the pathogenic functions of immune semaphorins, as well as the potential use of these molecules as diagnostic markers and therapeutic targets for the treatment of autoimmune diseases. [Nat Rev Rheumatol] Abstract

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OSE Immunotherapeutics to Resume Accrual in Phase III Clinical Trial of Tedopi^® in Advanced Non-Small Cell Lung Cancer Patients following Immune Checkpoint Inhibitor Treatment

OSE Immunotherapeutics announced that the Independent Data Monitoring Committee has recommended to the trial’s steering committee that accrual of the Tedopi^® Phase III trial for the treatment of advanced non-small cell lung cancer could resume with a specified new recruitment strategy focused on a subgroup of patients who have failed a previous treatment with PD-1/PD-L1 immune checkpoint inhibitors. [OSE Immunotherapeutics] Press Release

Seres Therapeutics Announces FDA Orphan Drug Designation for SER-287 in Treatment of Pediatric Ulcerative Colitis

Seres Therapeutics, Inc. announced that the FDA has granted Orphan Drug Designation to microbiome therapeutic candidate SER-287 for the treatment of ulcerative colitis in pediatric patients. [Seres Therapeutics, Inc.] Press Release

Investigation Finds Swedish Scientists Committed Scientific Misconduct

Two Swedish scientists have been found guilty of “misconduct in research” in a paper that they published in Science and later retracted. Their highly publicized work had suggested that tiny particles of plastic in the ocean harm fish. [Nature News] Editorial

Brexit “Breakthrough” Draws Praise from Science Policy Experts

In laboratories throughout the UK, researchers and administrators gave out a collective sigh of relief following a decision to allow EU nationals to remain after the country leaves the union in March 2019. [Nature News] Editorial

U.S. Science Groups Make Last-Minute Push to Influence Final Tax Deal

It wasn’t your typical graduate school experience. Eight graduate students, including doctoral students in anthropology and astrophysics at major U.S. universities, ended up in handcuffs after they refused to end a noisy protest outside the Washington, D.C., office of Speaker of the House of Representatives Paul Ryan. [ScienceInsider] Editorial

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