An Effective Approach to Prevent Immune Rejection of Human ESC-Derived Allografts Scientists established knockin human embryonic stem cells (hESCs) that constitutively express CTLA4-Ig and PD-L1 before and after differentiation, denoted CP hESCs. They then demonstrated that allogenic CP hESC-derived teratomas, fibroblasts, and cardiomyocytes are immune protected in humanized mice, while cells derived from parental hESCs are effectively rejected. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract IL-17 Regulates Systemic Fungal Immunity by Controlling the Functional Competence of NK Cells Scientists found that mice lacking interleukin (IL)-17 receptor signaling had a cell-intrinsic impairment in the development of functional NK cells, which accounted for the susceptibility of these mice to systemic fungal infection. [Immunity] Abstract | Graphical Abstract A Single Subset of Dendritic Cells Controls the Cytokine Bias of Natural Killer T Cell Responses to Diverse Glycolipid Antigens The authors showed that a single type of cell, the CD8α+ DEC-205+ dendritic cell, was mainly responsible for capturing and presenting a variety of different glycolipid antigens, including multiple forms of α-galactosylceramide that stimulate widely divergent cytokine responses. [Immunity] Full Article | Graphical Abstract The Circulating Proteinase Inhibitor α-1 Antitrypsin Regulates Neutrophil Degranulation and Autoimmunity Researchers investigated the ability of serum α-1 antitrypsin (AAT) to control tumor necrosis factor-α (TNF-α) biosynthesis and signaling in neutrophils and assessed whether AAT deficiency is a TNF-α-related disease. In vitro studies demonstrated that serum AAT coordinates TNF-α intracellular signaling and neutrophil degranulation of tertiary and secondary granules via modulation of ligand-receptor interactions. [Sci Transl Med] Abstract The Long Noncoding RNA Related Immunoregulatory lincRNA Regulates TNFα Expression through Its Interaction with Heterogenous Nuclear Ribonucleoprotein L Scientists used a custom microarray to identify large intergenic noncoding RNAs (lincRNAs) associated with activation of the innate immune response. A panel of 159 lincRNAs was found to be differentially expressed following innate activation of THP1 macrophages. [Proc Natl Acad Sci USA] Abstract | Press Release Lysine Deacetylase Inhibition Prevents Diabetes by Chromatin-Independent Immunoregulation and β-Cell Protection The authors demonstrated that the clinically well-tolerated lysine deacetylase inhibitors vorinostat and givinostat revert diabetes in the nonobese diabetic mouse model of type 1 diabetes and counteract inflammatory target cell damage by a mechanism of action consistent with transcription factor-rather than global chromatin-hyperacetylation. Vorinostat treatment increased the frequency of functional regulatory T-cell subsets and their transcription factors Gata3 and FoxP3 in parallel to a decrease in inflammatory dendritic cell subsets and their cytokines IL-6, IL-12, and TNF-α. [Proc Natl Acad Sci USA] Abstract | Press Release T Helper 2 and Regulatory T-Cell Cytokine Production by Mast Cells: A Key Factor in the Pathogenesis of IgG4-Related Disease Researchers analyzed paraffin-embedded sections of tissues from nine cases of IgG4-related submandibular gland disease, five cases of submandibular sialolithiasis, and six cases of normal submandibular gland in order to identify potential key players in the pathogenesis of IgG4-related disease. [Modern Pathol] Abstract Mesenchymal Stem Cells Reciprocally Regulate the M1/M2 Balance in Mouse Bone Marrow-Derived Macrophages Scientists hypothesized that mesenchymal stem cells (MSCs) may modulate the immunologic environment to accelerate regeneration. This study was designed to assess the functional relationship between the macrophage phenotype and MSCs. [Exp Mol Med] Full Article |