Tim-3 expression is induced by mycobacterial antigens and identifies tissue-resident subsets of MAIT cells from patients with tuberculosis.

Tissue-resident MAIT cells in tuberculous pleural effusions, the site of tuberculosis infection, were investigated in the study. Tim-3+CD69+CD103+ and CD39+CD69+CD103+ tissue-resident MAIT cell subsets were identified in tuberculous pleural effusions. Tim-3 expression in MAIT cells was greatly induced and CD39 expression was elevated following ex vivo stimulation with Mycobacterium tuberculosis antigens. Mycobacterial antigen-stimulated Tim-3+CD69+CD103+ tissue-resident MAIT cells had higher frequency of IFN-γ- and granzyme B-producing cells than Tim-3-CD69+CD103+ subset, while CD39+CD69+CD103+ MAIT cells had similar frequency of IFN-γ-positive cells but higher ratio of granzyme B-producing cells than CD39-CD69+CD103+ subset. Blocking of IL-2, IL-12p70 or IL-18 but not IL-15 led to significantly reduced expression of Tim-3 compared with isotype antibody control. In contrast, CD39 expression was not influenced by any of the cytokines tested. Tim-3+ MAIT cells had higher levels of lipid uptake and lipid content than Tim-3- cells. It is concluded that Tim-3+CD69+CD103+ tissue-resident MAIT cells were elevated in tuberculous pleural effusions and had higher capacity to produce effector molecules of IFN-γ and granzyme B.

PTEN-induced kinase 1 enhances the reparative effects of bone marrow mesenchymal stromal cells on mice with renal ischaemia/reperfusion-induced acute kidney injury.

Acute kidney injury (AKI) is a common severe acute syndrome caused by multiple factors and is characterized by a rapid decline in renal function during a short period. Bone marrow mesenchymal stromal cells (BMSCs) are effective in treating AKI. However, the mechanism of their beneficial effects remains unclear. PTEN-induced kinase 1 (PINK1) may play an important role in kidney tissue repair. In this study, we explored the effect of PINK1 overexpression on enhancing BMSC-mediated repair of AKI. In this study, ischaemia/reperfusion-induced AKI (IRI-AKI) in mice and a hypoxia-reoxygenation model in cells were established, and the indices were examined by pathology and immunology experiments. After ischaemia/reperfusion, PINK1 overexpression reduced apoptosis in injured kidney tissue cell, decreased T lymphocyte infiltration, increased macrophage infiltration, and alleviated the inflammatory response. PINK1 relieved the stress response of BMSCs and renal tubular epithelial cells (RTECs), reduced apoptosis, altered the release of inflammatory factors, and reduced the proliferation of peripheral blood mononuclear cells (PBMCs). In conclusion, BMSCs and RTECs undergo stress responses in response to hypoxia, inflammation and other conditions, and overexpressing PINK1 in BMSCs could enhance their ability to resist these stress reactions. Furthermore, PINK1 overexpression can regulate the distribution of immune cells and improve the inflammatory response. The regulation of mitochondrial autophagy during IRI-AKI maintains mitochondrial homeostasis and protects renal function. The results of this study provide new strategies and experimental evidence for BMSC-mediated repair of IRI-AKI.

Advances of research of Fc-fusion protein that activate NK cells for tumor immunotherapy.

The rapid development of bioengineering technology has introduced Fc-fusion proteins, representing a novel kind of recombinant protein, as promising biopharmaceutical products in tumor therapy. Numerous related anti-tumor Fc-fusion proteins have been investigated and are in different stages of development. Fc-fusion proteins are constructed by fusing the Fc-region of the antibody with functional proteins or peptides. They retain the bioactivity of the latter and partial properties of the former. This structural and functional advantage makes Fc-fusion proteins an effective tool in tumor immunotherapy, especially for the recruitment and activation of natural killer (NK) cells, which play a critical role in tumor immunotherapy. Even though tumor cells have developed mechanisms to circumvent the cytotoxic effect of NK cells or induce defective NK cells, Fc-fusion proteins have been proven to effectively activate NK cells to kill tumor cells in different ways, such as antibody-dependent cell-mediated cytotoxicity (ADCC), activate NK cells in different ways in order to promote killing of tumor cells. In this review, we focus on NK cell-based immunity for cancers and current research progress of the Fc-fusion proteins for anti-tumor therapy by activating NK cells.

The advantage of Sirolimus in amplifying regulatory B cells and regulatory T cells in liver transplant patients.

Sirolimus has been shown to ameliorate steroid-resistant rejection and induce long-term immune tolerance among liver transplant patients. However, the detailed mechanism of how Sirolimus achieve these advantages is still lacking. This study attempts to reveal some possible mechanisms by investigating regulatory B cells (Bregs), regulatory T cells (Tregs) and some cytokines in liver transplant recipients whose Tacrolimus was partially converted to Sirolimus. The results showed that CD19+CD24+CD38+Bregs and CD4+CD25+FoxP3+Tregs increased significantly during the first month after drug conversion (P < 0.01 and P < 0.05). The percentages of IL-10+Bregs and TGF-ß1+Bregs were also elevated (P < 0.05 and P < 0.01), and the same trend was observed in the levels of IL-10 and TGF-ß1 (P < 0.01 and P < 0.01). However, in the observation period, these investigated lymphocyte subsets and cytokines didn't change significantly in patients without Sirolimus usage. The incidence of biliary stenosis in the conversion group were significantly lower than that in the control group (P < 0.05). At the same time, in vitro experiments showed that Sirolimus could significantly amplify Bregs and Tregs (P < 0.01 and P < 0.01) while Tacrolimus did not show the amplifications effects. Sirolimus' function of amplifying Bregs was weakened, and its function of amplifying Tregs even disappeared after IL-10 and TGF-ß1 were neutralized. In conclusion, Sirolimus could amplify Bregs and Tregs among liver transplant recipient, which might be benefit to mitigate the immune response, decrease chances of rejection and alleviate biliary complication. IL-10 and TGF-ß1 may play important roles during this process.

[Research of Identify Spatial Object Using Spectrum Analysis Technique].

The high precision scattering spectrum of spatial fragment with the minimum brightness of 4.2 and the resolution of 0.5 nm has been observed using spectrum detection technology on the ground. The obvious differences for different types of objects are obtained by the normalizing and discrete rate analysis of the spectral data. Each of normalized multi-frame scattering spectral line shape for rocket debris is identical. However, that is different for lapsed satellites. The discrete rate of the single frame spectrum of normalized space debris for rocket debris ranges from 0.978% to 3.067%, and the difference of oscillation and average value is small. The discrete rate for lapsed satellites ranges from 3.118 4% to 19.472 7%, and the difference of oscillation and average value relatively large. The reason is that the composition of rocket debris is single, while that of the lapsed satellites is complex. Therefore, the spectrum detection technology on the ground can be used to the classification of the spatial fragment.