The Lymphoid Lineage-Specific Actin-Uncapping Protein Rltpr Is Essential for Costimulation via CD28 and the Development of Regulatory T Cells The authors found that Rltpr was a lymphoid cell-specific, actin-uncapping protein essential for costimulation via CD28 and the development of regulatory T cells. [Nat Immunol] Abstract Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T Helper 1 and T Helper 2 Cell Polarization Naive CD4+ T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, scientists generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hours of in vitro polarization toward T helper 1 and T helper 2 cell lineages. [Immunity] Abstract | Graphical Abstract Tob1 Plays a Critical Role in the Activation of Encephalitogenic T Cells in CNS Autoimmunity Investigators report that experimental autoimmune encephalomyelitis (EAE) in Tob1-/- mice was associated with augmented central nervous system (CNS) inflammation, increased infiltrating CD4+ and CD8+ T cell counts, and increased myelin-reactive Th1 and Th17 cells, with reduced numbers of regulatory T cells. [J Exp Med] Abstract | Press Release Shp1 Regulates T Cell Homeostasis by Limiting IL-4 Signals To define the T cell-intrinsic role of Shp1, researchers characterized mice with a T cell-specific Shp1 deletion (Shp1fl/fl CD4-cre). Surprisingly, thymocyte selection and peripheral TCR sensitivity were unaltered in the absence of Shp1. Instead, Shp1fl/fl CD4-cre mice had increased frequencies of memory phenotype T cells that expressed elevated levels of CD44. Activation of Shp1-deficient CD4+ T cells also resulted in skewing to the Th2 lineage and increased IL-4 production. [J Exp Med] Abstract Melanoma Immunotherapy Using Mature DCs Expressing the Constitutive Proteasome Since proteasomes generate peptides presented by HLA class I molecules, the authors hypothesized that mature melanoma antigen-loaded DCs engineered to process antigens through constitutive proteasomes would be superior inducers of antimelanoma immunity in vivo. [J Clin Invest] Full Article Dysfunctional CD39POS Regulatory T Cells and Aberrant Control of T Helper Type 17 Cells in Autoimmune Hepatitis Investigators described multiple CD39pos regulatory T cell defects that potentially contribute to the impaired immuno-regulation that is characteristic of autoimmune hepatitis. [Hepatology] Abstract Plasmid-Encoded Proinsulin Preserves C-Peptide while Specifically Reducing Proinsulin-Specific CD8+ T Cells in Type 1 Diabetes Scientists hypothesized that an engineered DNA plasmid encoding proinsulin (BHT-3021) would preserve β cell function in type 1 diabetes patients through reduction of insulin-specific CD8+ T cells. Proinsulin-reactive CD8+ T cells, but not T cells against unrelated islet or foreign molecules, declined in the BHT-3021 arm. No significant changes were noted in interferon-γ, interleukin-4 (IL-4), or IL-10 production in CD4 T cells. [Sci Transl Med] Abstract | Press Release IL-22-Producing Neutrophils Contribute to Antimicrobial Defense and Restitution of Colonic Epithelial Integrity during Colitis Using a dextran sodium sulfate-induced mouse model of acute colitis, the authors observed an interleukin (IL)-23-dependent up-regulation of IL-22 in the middle and distal colon at the onset of epithelial cell damage. This heightened IL-22 correlated with an influx of innate immune cells, suggesting an important role in colonic epithelial protection. Freshly isolated colon-infiltrating neutrophils produced IL-22 contingent upon IL-23 signaling, and IL-22 production was augmented by TNF-α. [Proc Natl Acad Sci USA] Abstract CC-Chemokine Receptor 8 Potentiates Donor Treg Survival and Is Critical for the Prevention of Murine Graft-versus-Host Disease Previous work suggested that early Treg migration into lymphoid tissue was important for graft-versus-host disease (GvHD) prevention. However, it is unclear how and where Tregs function longitudinally to affect GvHD. To better understand their mechanism of action, researchers studied two Treg-associated chemokine receptors in murine stem cell transplant models. [Blood] Abstract Downregulation of Stat3 in Melanoma: Reprogramming the Immune Microenvironment as an Anticancer Therapeutic Strategy Researchers investigated whether lentiviral (LV) delivery of Stat3-targeting short hairpin RNA (shRNA; LV-shStat3) to K1735-C4 melanoma cells modulates antitumor immunity. A single injection of LV-shStat3 in K1735-C4 tumors efficiently downregulated Stat3 in vivo and resulted in reduction of both vascular endothelial growth factor secretion and in myeloid-derived suppressor cell (MDSC) numbers. In contrast, the authors observed an increase in interleukin-6 and interferon-γ secretion, mature dendritic cells (DCs) and CD8+ T cells. Both DCs and CD8+ T cells displayed enhanced activity, whereas granulocytic MDSCs lost their suppressive capacity upon Stat3 downregulation. [Gene Ther] Abstract |