How the tumor microenvironment educates dendritic cells (DCs) to promote tumorigenesis remains largely unknown, and the role of tumor-derived exosomes (TEXs) in tumorigenesis is controversial. Here, we report that in addition to the activation of DCs, TEXs induce DCs to produce increased interleukin-6 (IL-6), which dramatically promotes tumor invasion by increasing signal transducer and activator of transcription 3 (STAT3)-dependent matrix metalloproteinases 9 transcription activity in tumor cells. HSP72 and HSP105 on the TEX surface induce IL-6 secretion of DCs in a TLR2- and TLR4-dependent manner. In addition, HSP72 and HSP105 are predominantly present on exosomes from sera of tumor patients but not healthy people, indicating their value in tumor prediction. Furthermore, TEXs are powerful activators of DCs, and the depletion of IL-6 converts TEXs from tumor promoters to tumor inhibitors . Therefore, our results reveal a novel mechanism for the TEX-mediated education of DCs and shed light on the conundrum that TEXs present by playing dual roles in tumorigenesis.

. Significance: Oral cancer is a quite common global health issue. Early diagnosis of cancerous and potentially malignant disorders in the oral cavity would significantly increase the survival rate of oral cancer. Previously reported smartphone-based images detection methods for oral cancer mainly focus on demonstrating the effectiveness of their methodology, yet it still lacks systematic study on how to improve the diagnosis accuracy on oral disease using hand-held smartphone photographic images. Aim: We present an effective smartphone-based imaging diagnosis method, powered by a deep learning algorithm, to address the challenges of automatic detection of oral diseases. Approach: We conducted a retrospective study. First, a simple yet effective centered rule image-capturing approach was proposed for collecting oral cavity images. Then, based on this method, a medium-sized oral dataset with five categories of diseases was created, and a resampling method was presented to alleviate the effect of image variability from hand-held smartphone cameras. Finally, a recent deep learning network (HRNet) was introduced to evaluate the performance of our method for oral cancer detection. Results: The performance of the proposed method achieved a sensitivity of 83.0%, specificity of 96.6%, precision of 84.3%, and of 83.6% on 455 test images. The proposed “center positioning” method was about 8% higher than that of a simulated “random positioning” method in terms of score, the resampling method had additional 6% of performance improvement, and the introduced HRNet achieved slightly better performance than VGG16, ResNet50, and DenseNet169, with respect to the metrics of sensitivity, specificity, precision, and . Conclusions: Capturing oral images centered on the lesion, resampling the cases in training set, and using the HRNet can effectively improve the performance of deep learning algorithm on oral cancer detection. The smartphone-based imaging with deep learning method has good potential for primary oral cancer diagnosis.

Osteogenesis on the interface between the implant and host bone is a synergistic processing of multiple systems involved in immune response, angiogenesis, osteogenesis, etc. However, regulation of the osteoimmune microenvironment on the implant surface to accelerate the osteogenesis through manipulating the polarization of macrophage phenotype is still beginning to be explored. We here demonstrate that macrophage phenotype is able to be regulated by decoration of mineralized collagen (MC) coating on the titanium implant surface via triggering the integrin-related cascade pathway of macrophages. Furthermore, regulation of the macrophage polarization and construction of the osteoimmune microenvironment by MC coating would subsequently accelerate the osteogenic differentiation of the mesenchymal stem cells. This work therefore emphasizes the importance of the osteoimmune microenvironment on osteogenesis and provides a promising strategy to improve the osteointegration of implants.

Salmeterol is a long-acting b2-agonist that activates adenylate cyclase, causing long-lasting bronchodilation and has been used for many years to control asthma. However, little information is available about the immunoregulatory effects of salmeterol. We found that salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6. Dendritic cells (DCs) are antigen-presenting cells and act as sentinels in the airway. We found that salmeterol (10 25 mol/l) reduced the inflammation caused by lipopolysaccharide (0.1 mg/ml) in activated murine bone marrow-derived DCs. Moreover, western blots demonstrated that this protective effect was mediated partially by inhibiting signaling through the nuclear factor-kappa B (NF-kB), mitogen-activated protein kinase (MAPK) pathways and dramatically decreased levels of p-ERK. We suggest that salmeterol regulates the inflammation of allergen-induced asthma by modulating DCs. In conclusion, we provide evidence that DCs are the target immune cells responsible for the action of salmeterol against asthma.

The immune balance of the respiratory tract is strictly regulated. Extracellular vesicles (EVs) have been reported to participate in maintaining the immune balance in the intestinal tract, but whether they are involved in regulation of the immune balance in the respiratory tract has yet to be revealed. In this study, we found that physiological EVs from lungs of WT mice (L-EVs) could be isolated, which contained the immunosuppressive cytokines TGF-β1 and IL-10. Among L-EV subsets, only the CD8αCD11c EV subset was positive for TGF-β1 and IL-10 and could inhibit CD4 T cell proliferation via TGF-β1 in vitro and relieve murine asthmatic symptoms. Mechanistically, L-EVs were effective at inhibiting OVA peptide-specific CD4 T cell proliferation in a TGF-β1- and IL-10-dependent manner. In addition, they could prevent CD4 T cells from hilar lymph nodes from secreting IL-4, IL-9, and IL-17A via IL-10 ex vivo, suggesting inhibition of Th2, Th9, and Th17 cell responses. Altogether, our results indicate that EVs from the lungs are involved in control of the immune balance in the respiratory tract, which reveals a novel mechanism in the maintenance of respiratory tract immune homeostasis.