Abnormal subretinal neovascularization is a characteristic of vision-threatening retinal diseases, including macular telangiectasia (MacTel) and retinal angiomatous proliferation (RAP). Subretinal neovascular tufts and photoreceptor dysfunction are observed in very-low-density lipoprotein receptor (Vldlr-/-) mutant mice. These changes mirror those observed in patients with MacTel and RAP, but the pathogenesis is largely unknown. In this study, we show that retinal microglia were closely associated with retinal neovascular tufts in Vldlr-/- mice and retinal tissue from patients with MacTel; ablation of microglia/macrophages dramatically prevented formation of retinal neovascular tufts and improved neuronal function, as assessed by electroretinography. Vldlr-/- mice with retinal pigmented epithelium-specific (RPE-specific) Vegfa had greatly reduced subretinal infiltration of microglia/macrophages, subsequently reducing neovascular tufts. These findings highlight the contribution of microglia/macrophages to the pathogenesis of neovascularization, provide valuable clues regarding potential causative cellular mechanisms for subretinal neovascularization in patients with MacTel and RAP and suggest that targeting microglia activation may be a therapeutic option in these diseases.Acute graft versus host disease (aGvHD) remains a major impediment to successful allogeneic hematopoietic cell transplantation (allo-HCT). To solve this problem, a greater knowledge of factors that regulate the differentiation of donor T cells toward cytotoxic cells or Tregs is necessary. We report that the β2-adrenergic receptor (β2-AR) is critical for regulating this differentiation and that its manipulation can control aGvHD without impairing the graft-versus-tumor (GvT) effect. Donor T cell β2-AR expression and signaling is associated with decreased aGvHD when compared with recipients of β2-AR-/- donor T cells. We determined that β2-AR activation skewed CD4+ T cell differentiation in vitro and in vivo toward Tregs rather than the T helper 1 (Th1) phenotype. Treatment of allo-HCT recipients with a selective β2-agonist (bambuterol) ameliorated aGvHD severity. This was associated with increased Tregs, decreased cytotoxic T cells, and increased donor BM-derived myeloid-derived suppressor cells (MDSCs) in allogeneic and humanized xenogeneic aGvHD models. β2-AR signaling resulted in increased Treg generation through glycogen synthase kinase-3 activation. Bambuterol preserved the GvT effect by inducing NKG2D+ effector cells and central memory T cells. These data reveal how β-AR signaling can be targeted to ameliorate GvHD severity while preserving GvT effect.Background HVTN 098, a randomized, double-blind, placebo-controlled trial, evaluated the safety, tolerability and immunogenicity of PENNVAX®-GP HIV DNA vaccine, administered with or without plasmid IL-12 (pIL-12), via intradermal (ID) or intramuscular (IM) electroporation (EP) in healthy, HIV-uninfected adults. The study tested whether PENNVAX®-GP delivered via ID/EP at 1/5th the dose could elicit equivalent immune responses to delivery via IM/EP, and if inclusion of pIL-12 provided additional benefit. Methods Participants received DNA encoding HIV-1 env/gag/pol in three groups 1.6mg ID (ID no IL-12 group, n=20), 1.6mg ID + 0.4mg pIL-12 (ID+IL-12 group, n=30), 8mg IM + 1mg pIL-12 (IM+IL-12 group, n=30) or placebo (n=9) via EP at 0, 1, 3 and 6 months. Results of cellular and humoral immunogencity assessments are reported. Results Following vaccination, the frequency of responders (response rate) to any HIV protein based on CD4+ T-cells expressing IFN-γ and/or IL-2 was 96% for both the ID+IL-12 and IM+IL-12 grory-ˇCDC Clinical Trials Unit], UM AI069511 [University of Rochester HIV/AIDS Clinical Trials Unit], UM1 AI069439 77 [Vanderbilt Clinical Trial Unit], UM1 AI069481 [Seattle-ˇLausanne Clinical Trials Unit] and HVDDT Contract HHSN2722008000063C (Inovio Pharmaceuticals). This work was also supported, in part, by IPCAVD award U19 AI09646-ˇ03 (DBW) and NIH award P01 AI120756 (GDT). The opinions expressed in this article are those of the authors and do not necessarily represent the official views of the NIAID or the National Institutes of Health (NIH).Graft-versus-host disease (GVHD) remains an important cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (allo-HCT). For decades, GVHD prophylaxis has included calcineurin-inhibitors, despite their incomplete efficacy and impairment of graft-versus-leukemia (GVL). Distinct from pharmacologic immune suppression, we have developed a novel, human CD83-targeted chimeric antigen receptor (CAR) T cell for GVHD prevention. CD83 is expressed on allo-activated, conventional CD4+ T cells (Tconv) and proinflammatory dendritic cells (DC); which are both implicated in GVHD pathogenesis.  https://www.selleckchem.com/products/ots964.html  Human CD83 CAR T cells eradicate pathogenic CD83+ target cells, significantly increase the ratio of regulatory T cells (Treg) to allo-activated Tconv, and provide durable prevention of xenogeneic GVHD. CD83 CAR T cells are also capable of treating xenogeneic GVHD. We show human, acute myeloid leukemia (AML) expresses CD83 and myeloid leukemia cell lines are readily killed by CD83 CAR T cells. Human CD83 CAR T cells are a promising cell-based approach to prevent two critical complications of allo-HCT; GVHD and relapse. Thus, human CD83 CAR T cells warrant clinical investigation in GVHD prevention and treatment, as well as targeting CD83+ AML.Abnormal expression of long noncoding RNA (lncRNA) is involved in human cancers, including colorectal cancer (CRC). However, their functional mechanism is largely unknown. In this study, we explored the roles of lncRNA SOCS2-AS1 in modulating CRC progression. We showed that SOCS2-AS1 was lowly expressed in CRC tissues and cells. SOCS2-AS1 downregulation predicted a poor prognosis in patients with CRC. SOCS2-AS1 overexpression significantly suppressed CRC cell proliferation, colony formation, EdU incorporation, cell-cycle, migration and invasion in vitro while SOCS2-AS1 knockdown led to an opposite phenotype. SOCS2-AS1 overexpression inhibited CRC growth and metastasis in vivo. Mechanistically, we discovered that SOCS2-AS1 was positively correlated with SOCS2 expression in CRC tissues. SOCS2-AS1 contributes to SOCS2 expression through restraining miR-1264. Additionally, we showed that SOCS2 silencing abrogated the suppressive effects of SOCS2-AS1 overexpression. Taken together, our results identified a novel regulatory loop in which SOCS2-AS1/miR-1264/SOCS2 axis suppresses CRC progression.