The fates of dendritic cells (DCs) after antigen presentation have been studied extensively, but the influence of lymphoid microenvironments on DCs is mostly unknown. Here, using splenic stromal cells to mimic the immune microenvironment, we show that contact with stromal cells promoted mature DCs to proliferate in a fibronectin-dependent way and that both stromal cell contact and stromal cell-derived transforming growth factor-beta induced their differentiation into a new regulatory DC subset. We have identified an in vivo counterpart in the spleen with similar phenotype and functions. These differentiated DCs secreted nitric oxide, which mediated the suppression of T cell proliferation in response to antigen presentation by mature DCs. Thus, our findings identify an important mechanism by which the microenvironment regulates immune responses.

Metal halide perovskite semiconductors possess outstanding characteristics for optoelectronic applications including but not limited to photovoltaics. Low-dimensional and nanostructured motifs impart added functionality which can be exploited further. Moreover, wider cation composition tunability and tunable surface ligand properties of colloidal quantum dot (QD) perovskites now enable unprecedented device architectures which differ from thin-film perovskites fabricated from solvated molecular precursors. Here, using layer-by-layer deposition of perovskite QDs, we demonstrate solar cells with abrupt compositional changes throughout the perovskite film. We utilize this ability to abruptly control composition to create an internal heterojunction that facilitates charge separation at the internal interface leading to improved photocarrier harvesting. We show how the photovoltaic performance depends upon the heterojunction position, as well as the composition of each component, and we describe an architecture that greatly improves the performance of perovskite QD photovoltaics.

(FA-acetate, 99%) were purchased from Sigma-Aldrich and used as received unless otherwise specified. CsPbI3 QD synthesis. The synthesis was performed following the method reported in our previous publications with slight modification. 1,2 First, 20 mL of ODE is mixed with 1.25 mL of OA containing 0.407 g of Cs2CO3. This was degassed at 120°C for 20 min under vacuum in a three-neck flask to form Cs-oleate. The Cs-oleate precursor was kept under N2 instead of vacuum after Cs2CO3 was completely dissolved in the solution. Then the PbI2 precursor was formed by mixing 0.5 g of PbI2 and 25 mL of ODE in a three-neck flask and heated at 120°C for 20 min under vacuum. A preheated mixture of OA and OAm (135°C, 2.5 mL each) was transferred into the PbI2 solution that was kept at 120°C under vacuum. After the PbI2 completely dissolved in the solution, the reaction flask was heated to the desired temperature (140, 160, or 180°C) under flowing N2. Then 2 mL of the Cs-oleate precursor was swiftly injected into the reaction flask. In general, smaller nanocrystals are obtained with lower growth and larger are obtained with higher temperature, but some sizes overlap this trend when using the size selective precipitation. Immediately after the reaction, the mixture was quenched by submerging the flask into an ice bath within 3 s after the injection. After cooling to room temperature, 70 mL of MeOAc was added into the colloidal solution and the mixed solution was centrifuged at 7500 rpm for 5 min.

Although many studies have addressed the prognostic value of programmed cell death-ligand 1 (PD-L1) expression in lung cancer, the results remain controversial. A systematic search of the PubMed, EMBASE, and Cochrane Library databases was performed to identify the correlation between PD-L1 expression and driver mutations and overall survival (OS). This meta-analysis enrolled a total of 11,444 patients for 47 studies, and the pooled results showed that increased PD-L1 expression was associated with poor prognosis (HR = 1.40, 95% CI: 1.19–1.65, P < 0.001). In subgroup analysis stratified according to histology types, the pooled results demonstrated that increased PD-L1 expression was an unfavorable prognostic factor for non-small cell lung cancer (NSCLC) (HR = 1.26, 95% CI: 1.05–1.52, P = 0.01) and pulmonary lymphoepithelioma-like carcinoma (LELC) (HR = 3.04, 95% CI: 1.19–7.77, P = 0.02), rather than small cell lung cancer (SCLC) (HR = 0.62, 95% CI: 0.27–1.39, P = 0.24). The pooled ORs indicated that PD-L1 expression was associated with gender, smoking status, histology, differentiation, tumour size, lymph nodal metastasis, TNM stage and EGFR mutation. However, PD-L1 expression was not correlated with ALK rearrangement and KRAS mutations.

SUMMARYToll-like receptors (TLR) are sentinel receptors capable of recognizing pathogen-associated molecule patterns (PAMP) such as lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are major receptors for Gram-positive and Gram-negative bacterial cell wall components, respectively. TLR9 is necessary for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and increased ability to activate T cells. However, little is known regarding the regulation of TLR gene expression in mouse DC. In this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with significantly increased production of tumour necrosis factor-a induced by LPS plus CpG ODN. While inhibition of extracellular signal-related kinase and NF-kB activation suppressed the up-regulation of the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS might promote the overall responses of DC to bacteria and help to explain the synergy between LPS and other bacterial products in the induction of cytokine production.

Regulatory dendritic cells (DCs) have been reported recently, but their origin is poorly understood. Our previous study demonstrated that splenic stroma can drive mature DCs to proliferate and differentiate into regulatory DCs, and their natural counterpart with similar regulatory function in normal spleens has been identified. Considering that the spleen microenvironment supports hematopoiesis and that hematopoietic stem cells (HSCs) are found in spleens of adult mice, we wondered whether splenic microenvironment could differentiate HSCs into regulatory DCs. In this report, we demonstrate that endothelial splenic stroma induce HSCs to differentiate into a distinct regulatory DC subset with high expression of CD11b but low expression of Ia. CD11b hi Ia lo DCs secreting high levels of TGF-␤, IL-10, and NO can suppress T-cell proliferation both in vitro and in vivo. IntroductionDendritic cells (DCs) play crucial roles in the initiation and regulation of immune responses. 1,2 The ability of DCs to initiate immune responses or induce tolerance is strictly dependent on their maturation state or subsets. It has been reported that immature DCs that are deficient of costimulatory molecules can induce T-cell anergy, generate regulatory T (Treg) cells, and promote alloantigen-specific tolerance. Several types of DCs with negative regulatory functions have been reported. 3 Most regulatory DCs are prepared in vitro using immunosuppressive cytokines, such as IL-10 and TGF-␤. [4][5][6] However, this may not reflect the real differentiation of regulatory DCs in the immune microenvironment in vivo.The development of hematopoietic cells in vivo occurs in the context of microenvironment or niche, 7 which consists of many types of stromal cells, such as fibroblasts, macrophages, endothelium cells, and adipose cells. The microenvironment provides various signals for hematopoietic cell development. 7 Different microenvironments support different types of cell differentiation. The spleen is an important lymphoid organ, and the mouse spleen maintains hematopoietic function throughout life. 8 Furthermore, hematopoietic stem cells (HSCs) are found in spleens of adult mice. 8 Therefore, it is conceivable that HSCs in the spleen may differentiate into different immune cells in situ.Splenic stromal cells cultured in vitro could mimic the splenic microenvironment in vivo to some extent, despite their differences in some constituents. There is evidence that long-term cultured splenic stromal cells can support the development of dendritic-like cells in the absence of exogenous cytokines, and the dendritic-like cells have the phenotype and function of DCs, 9-13 strongly suggesting that splenic microenvironment could induce hematopoietic progenitors to differentiate directly into DCs. Stromal cells cultured in vitro consist of multiple components. Purification of the various components will help to study the role of specific cell type in the induction of DCs. We established the method of preparing endothelial splenic stroma cells (ESSCs) and i...

TNF-α-related apoptosis-inducing ligand (TRAIL) is characterized by its preferential induction of apoptosis of tumor cells but not normal cells. Dendritic cells (DCs), besides their role as APCs, now have been demonstrated to exert cytotoxicity or cytostasis on some tumor cells. Here, we report that both human CD34+ stem cell-derived DCs (CD34DCs) and human CD14+ monocyte-derived DCs (MoDCs) express TRAIL and exhibit cytotoxicity to some types of tumor cells partially through TRAIL. Moderate expression of TRAIL appeared on CD34DCs from the 8th day of culture and was also seen on freshly isolated monocytes. The level of TRAIL expression remained constant until DC maturation. TRAIL expression on immature CD34DCs or MoDCs was greatly up-regulated after IFN-β stimulation. Moreover, IFN-β could strikingly enhance the ability of CD34DCs or MoDCs to kill TRAIL-sensitive tumor cells, but LPS did not have such an effect. The up-regulation of TRAIL on IFN-β-stimulated DCs partially contributed to the increased cytotoxicity of DCs. Pretreatment of TRAIL-sensitive tumor cells with caspase-3 inhibitor could significantly increase their resistance to the cytotoxicity of IFN-β-stimulated DCs. In contrast, NF-κB inhibitor could significantly increase the sensitivity of tumor cells to the killing by nonstimulated or LPS-stimulated DCs. Our studies demonstrate that IFN-β-stimulated DCs are functionally cytotoxic. Thus, an innate mechanism of DC-mediated antitumor immunity might exist in vivo in which DCs act as effectors to directly kill tumor cells partially via TRAIL. Subsequently, DCs act as APCs involved in the uptake, processing, and presentation of apoptotic tumor Ags to cross-prime CD8+ CTL cells.

An artificial nanofluidic diode system is prepared, mimicking the light-gated and pH-tunable ion channels that play an important role in life sciences. When UV light is off, the nanochannel is in the closed state, analogous to a resistance. Under UV light irradiation and at pH 7, the current flows from the tip to the base, analogous to a diode; at pH 3, the situation (and the diode) is reversed.