Immune Regulation News Volume 5.33 | Aug 30 2013

Stabilization of the Transcription Factor Foxp3 by the Deubiquitinase USP7 Increases Treg-Cell-Suppressive Capacity
Scientists demonstrated that the expression of the transcription factor Foxp3 can be regulated through the polyubiquitination of multiple lysine residues, resulting in proteasome-mediated degradation. Expression of the deubiquitinase USP7 was found to be upregulated and active in regulatory T (Treg) cells, being associated with Foxp3 in the nucleus. [Immunity] Abstract | Graphical Abstract

Up-Regulation of PD-L1, IDO, and T_regs in the Melanoma Tumor Microenvironment Is Driven by CD8⁺ T Cells
Although evidence for an active immune response, including infiltration with CD8⁺ T cells, can be found in a subset of patients, those tumors are nonetheless not immunologically rejected. The authors showed that it is the subset of T cell-inflamed tumors that showed high expression of three defined immunosuppressive mechanisms: indoleamine-2,3-dioxygenase (IDO), PD-L1/B7-H1, and FoxP3⁺ regulatory T cells (T_regs), suggesting that these inhibitory pathways might serve as negative feedback mechanisms that followed, rather than preceded, CD8⁺ T cell infiltration. [Sci Trans Med] Abstract

Complement Modulates the Cutaneous Microbiome and Inflammatory Milieu
Scientists revealed an interactive role for complement in cutaneous host-microbiome interactions. Inhibiting signaling of the complement component C5a receptor altered the composition and diversity of the skin microbiota as revealed by deep sequencing of the bacterial 16S rRNA gene. [Proc Natl Acad Sci USA] Abstract | Press Release

Expression of the Immune Regulator Tripartite-Motif 21 Is Controlled by IFN Regulatory Factors
The authors demonstrated that IFNs induce Tripartite-motif 21 (Trim21) expression in immune cells via IFN regulatory factors and that IFN-α and IFN-β are the most potent inducers of Trim21. [J Immunol] Abstract

Mbd2 Promotes Foxp3 Demethylation and T-Regulatory Cell Function
Conserved CpG dinucleotides in the regulatory T (Treg)-specific demethylated region upstream of Foxp3 are demethylated only in stable, thymic-derived Foxp3+ Tregs. Since methyl-binding domain (Mbd) proteins recruit histone-modifying and chromatin-remodeling complexes to methylated sites, the authors tested whether targeting of Mbd2 might promote demethylation of Foxp3 and thereby promote Treg numbers or function. [Mol Cell Biol] Abstract

PARP-1 Controls Immunosuppressive Function of Regulatory T Cells by Destabilizing Foxp3
Investigators showed that Poly (ADP-ribose) polymerase-1 (PARP-1) regulates the suppressive function of CD4⁺CD25⁺Foxp3⁺ regulatory T cells. [PLoS One] Full Article

Extensive Cooperation of Immune Master Regulators IRF3 and NFκB in RNA Pol II Recruitment and Pause Release in Human Innate Antiviral Transcription
To investigate RNA polymerase II (Pol II) recruitment and elongation in the human antiviral gene regulatory network, a comprehensive genome-wide analysis was conducted during the initial phase of virus infection. Results reveal extensive integration of interferon regulatory factor 3 (IRF3) and nuclear factor κB (NFκB) with Pol II and associated machinery and implicate partners for antiviral transcription. [Cell Rep]
Full Article | Graphical Abstract

Dendritic Cells and Other Innate Determinants of T Helper Cell Polarization
Recent studies have demonstrated that the innate immune system functions to direct the adaptive immune response, not only through antigen presentation but also by providing the key signals for the differentiation of naive CD4⁺ T cells into functionally distinct T helper cell subtypes. [Trends Immunol] Abstract

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Opexa Announces Issuance of 50th Patent for T-Cell Immunotherapy Platform
Opexa Therapeutics, Inc. announced that several key patents have issued, further strengthening the Company’s proprietary technology for the development of patient-specific immunotherapies. [Opexa Therapeutics, Inc.] Press Release

Cellular Biomedicine Group Announces Completion of Patient Enrollment for Phase I Clinical Trial for Liver Cancer
Cellular Biomedicine Group announced that it has completed patient enrollment for its Phase I trial to evaluate the safety and preliminary efficacy of Tumor Stem Cell Specific Dendritic Cell therapy for hepatocellular carcinoma, the most common type of liver cancer. [Cellular Biomedicine Group] Press Release

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