Search

Abstract Background The therapeutic effect of adoptive infusion of specific thymus-derived invariant natural killer T (iNKT) cells in a mouse model of rheumatoid arthritis (RA) was observed, and the mechanism of cellular immunotherapy was preliminarily explored. Methods Thymus-derived iNKT cells were infused to RA model mice, with α-GalCer as a positive control. Then, ankle swelling was examined, as well as inflammatory cell infiltration to the joint tissue (hematoxylin-eosin [H&E] staining). Flow cytometry (FCM) was used to assess iNKT cell and helper T lymphocyte (Th) subsets. Serum cytokine levels were determined with cytometric bead array (CBA), with protein expression levels of related transcription factors assessed by Western blot. Results The joint swelling in RA model animals were significantly improved in the cell therapy and α-GalCer positive control groups (P < 0.05). In addition, iNKT frequencies in peripheral blood, the thymus and spleen were increased significantly (P < 0.05). Meanwhile, iNKT1 subset frequencies in the thymus and spleen were decreased, as well as splenic Th1 and Th17 cell subset rates, and serum TNF-α, IFN-γ and IL-6 levels. The rates of iNKT2 and Th2 subsets as well as IL-4 and IL-10 levels were increased (P < 0.05). Thymus GATA-3 and splenic PLZF protein levels were increased (P < 0.05). Conclusions Adoptive infusion of thymus-derived iNKT cells exerts therapeutic effects in RA mice by increasing iNKT frequency, altering the proportions of iNKT cell subsets, correcting Th cell subset imbalance and reducing the amounts of inflammatory cytokines. Graphical abstract Unlabelled Image Highlights • The iNKT1 involved in and iNKT2 suppression of inflammatory response in RA. • Adoptive infusion of iNKT can correct the immune imbalance caused by Th1 and Th17. • iNKT therapy promotes Th0 to Th2 differentiation via up-regulating GATA3 expression. [ABSTRACT FROM AUTHOR]

Unmanned Aerial Vehicle (UAV) applications at low-volume using fine and very fine size droplets have been adopted in several commercial spray scenarios allowing water-saving and high-efficiency operation in delivery of pesticides. However, spray drift associated with UAV applications, especially for fine droplets generated from spinning disk nozzles, has not been fully understood, raising environmental and regulatory concerns. The objectives of this study were to compare the drift potential of three different volume median diameter (VMD, or Dv 0.5) of 100, 150 and 200 μm from a commercial quadcopter equipped with centrifugal nozzles exposed to different wind speeds under field conditions. Prior to field test, the droplet size of the centrifugal nozzle was measured by a laser-diffraction particle-size analyzer. The results showed that the relationship between rotation speed and Dv 0.5 agrees with the negative power function. Field tests found that the deposition at 12 m downwind direction decreased by an order of magnitude compared with the average deposition within the in-swath zone. The deposition of almost all the treatments at 50 m downwind is lower than the detection limits of 0.0002 μL/cm2. Based on the results from this study, the drift distance of this specific very popular UAV model is much less than that of manned aerial applicators. Based on the predicted equation (R2 = 0.83), the detected drift amount increased with increasing wind speed and decreasing Dv 0.5. This work provides basic information to quantify the effect of wind speeds and droplet sizes on UAV spray drift potential which supports on-going regulatory guideline development for spray buffer zone and drift risk assessment protocols. Unlabelled Image • When the rotation speed of the centrifugal nozzle increased from 2000 rpm to 17,000 rpm, the droplet size category changed from Extremely Coarse to Fine. • The deposition at 12 m downwind generally decreases by an order of magnitude compared with the in-swath zone. • A downwind prediction equation for the UAV sprayer was formulated to predict the expected magnitude of the deposited drift. • Based on the test results, the drift distance of the tested UAV model is much less than that of manned aerial applicators. [ABSTRACT FROM AUTHOR]

• α-GalCer activates iNKT10 cells of adipose tissue by subcutaneous injection. • iNKT10 cells promote M2 macrophage polarization in adipose tissue. • Activation of iNKT10 and M2 macrophages improves inflammation of adipose tissue. The role of iNKT cells was investigated in chronic adipose tissue inflammation in obese mice after administration of α-GalCer in different pathways. C57BL/6J mice were fed high-fat diet (HFD) for 12 weeks to establish the obese mouse model. The pathology of adipose tissue was observed by H&E staining. The rates of iNKT cells, macrophages and cell subsets in adipose tissue were detected by FCM. Cytokine levels in serum and adipose tissue lymphocyte-stimulated supernatants were assessed with the CBA kit. The expression levels of related transcription factor in adipose tissue were detected by Western blot. The proportions of iNKT cells, iNKT10 cells and M2 macrophages were decreased, while those of iNKT1 and M1 macrophages were increased in adipose tissue of HFD-fed mice. The expression levels of the related transcriptional proteins E4BP4 and Arg-1 were decreased while iNOS expression was increased in adipose tissue. Administration of α-GalCer by subcutaneous injection resulted in increased rates of iNKT10 cells and M2 macrophages, and decreased amounts of M1 macrophages in adipose tissue of HFD-fed mice. The expression of E4BP4 and Arg-1 were up-regulated, but iNOS was down-regulated. Meanwhile, infiltration of inflammatory cells into adipose tissue was further reduced. The imbalance between the proportions of iNKT1 and iNKT10 cells may be involved in the development of chronic inflammation in obese adipose tissue. Administration of α-GalCer by subcutaneous injection in HFD-fed mice activates adipose tissue iNKT10 cells, which promote M2 macrophage polarization and improve chronic inflammation in obese adipose tissue. [ABSTRACT FROM AUTHOR]

The existence of association between the subpopulation of iNKT cells with different functions and nonalcoholic fatty liver disease has not been confirmed. To investigative the role of iNKT cells in the pathogenesis of nonalcoholic fatty liver disease, we established a non-alcoholic fatty liver model by feeding C57BL/6J mice for 12 weeks with a high-fat diet and injecting α-GalCer through different routes to activate hepatic iNKT cells. The liver of the mice fed a high-fat diet (HFD) had severe hepatic steatosis appearance, elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines in the liver, and high serum levels of TC, LDL, HDL, and ALT. Our results showed that the percentage of iNKT cells in the liver of the HFD-fed mice was lower than that of the control mice. The expression levels of the related transcription factor of T-bet increased but that of GATA-3 decreased in the HFD-fed mice. The administration of α-GalCer by intraperitoneal injection resulted in increasing of hepatic iNKT and iNKT2 cells but decreasing of hepatic iNKT1 cells, and the expression of GATA-3 and anti-inflammatory cytokine (IL-4) was increased in the liver, and hepatic steatosis was ameliorated in the HFD-fed mice. The administration of α-GalCer by subcutaneous injection resulted in a decrease in hepatic iNKT and iNKT2 and an augmentation of hepatic iNKT1 cells. However, hepatic steatosis was not significantly improved. We concluded that the intraperitoneal injection with α-GalCer effectively improved hepatic steatosis, according to increasing the number of hepatic iNKT2 cells. The precise mechanism requires further exploration. Unlabelled Image • The number of hepatic iNKT cells is reduced in model mice of NAFLD. • α-GalCer activates hepatic iNKT1 cells by subcutaneous injection. • α-GalCer activates hepatic iNKT2 cells by intraperitoneal injection. • Activation of hepatic iNKT2 effectively improves hepatic steatosis. [ABSTRACT FROM AUTHOR]