Role of dendritic cells in the host response to biomaterials and their signaling pathways.

Strategies to enhance, inhibit, or qualitatively modulate immune responses are important for diverse biomedical applications such as vaccine adjuvant, drug delivery, immunotherapy, cell transplant, tissue engineering, and regenerative medicine. However, the clinical efficiency of these biomaterial systems is affected by the limited understanding of their interaction with complex host microenvironments, for example, excessive foreign body reaction and immunotoxicity. Biomaterials and biomedical devices implanted in the body may induce a highly complicated and orchestrated series of host responses. As macrophages are among the first cells to infiltrate and respond to implanted biomaterials, the macrophage-mediated host response to biomaterials has been well studied. Dendritic cells (DCs) are the most potent antigen-presenting cells that activate naive T cells and bridge innate and adaptive immunity. The potential interaction of DCs with biomaterials appears to be critical for exerting the function of biomaterials and has become an important, developing area of investigation. Herein, we summarize the effects of the physicochemical properties of biomaterials on the immune function of DCs together with their receptors and signaling pathways. This review might provide a complete understanding of the interaction of DCs with biomaterials and serve as a reference for the design and selection of biomaterials with particular effects on targeted cells. STATEMENT OF SIGNIFICANCE: Biomaterials implanted in the body are increasingly applied in clinical practice. The performance of these implanted biomaterials is largely dependent on their interaction with the host immune system. As antigen-presenting cells, dendritic cells (DCs) directly interact with biomaterials through pattern recognition receptors (PRRs) recognizing "biomaterial-associated molecular patterns" and generate a battery of immune responses. In this review, the physicochemical properties of biomaterials that regulate the immune function of DCs together with their receptors and signaling pathways of biomaterial-DC interactions are summarized and discussed. We believe that knowledge of the interplay of DC and biomaterials may spur clinical translation by guiding the design and selection of biomaterials with particular effects on targeted cell for tissue engineering, vaccine delivery, and cancer therapy.

Effect of TIPE1 on Immune Function of Dendritic Cells and Its Signaling Pathway in Septic Mice.

Dendritic cell (DC) dysfunction plays a pivotal role in sepsis-induced immunosuppression. Tumor necrosis factor α (TNF-α)-induced protein 8 like-1 (TIPE1), a new member of the tumor necrosis factor α-induced protein 8 family, may be related to cell death. The aim of the present study was to elucidate the effect of TIPE1 on the immune function of DCs and its regulatory mechanism via PD-L1/PD-1 signaling in mice. Sepsis was induced in adult C57BL/6 male mice via cecal ligation and puncture. In vitro, we found that expression of CD80, CD86, and major histocompatibility complex class II in DCs and levels of cytokines, including tumor necrosis factor α and interleukin 12p40, were elevated; similarly, T-cell proliferation and differentiation were promoted when the gene expressing TIPE1 was silenced. Next, we examined the in vivo role of TIPE1 in a cecal ligation and puncture animal model system. Flow cytometry of the immune functional status in DCs revealed negative regulation of TIPE1 on DC maturation, as well as activation. Moreover, changes in PD-L1/PD-1 levels confirmed the negative effect of TIPE1 in DCs. Collectively, we report that TIPE1 might exert negative regulation in sepsis, at least in part by inhibiting DC maturation and subsequent T-cell-mediated immunity via PD-L1/PD-1 signaling.

The potential mechanism of extracellular high mobility group box-1 protein mediated p53 expression in immune dysfunction of T lymphocytes.

In the present study, we examined the activity of p53 protein in Jurkat cells treated with high mobility group box-1 protein (HMGB1), thereafter we investigated the mechanism of extracellular HMGB1 mediated p53 expression in immune dysfunction of T lymphocytes. mRNA expression of p53, mdm2, and p21 was determined by Real-time reverse transcription-polymerase chain reaction(RT-PCR). The apoptotic rate of Jurkat cells was analyzed by flow cytometry. Expressions of bcl-2, bax, caspase-3, phosphorylated (p) extracellular signal-regulated kinase (ERK)1/2, ERK1/2, p-p38 mitogen-activated protein kinase (MAPK), p38 MAPK, and p-c-jun amino-terminal kinase (JNK)1/2 and JNK1/2 were simultaneously determined by Western blotting. After treatment with HMGB1 (100 ng/ml or 1000 ng/ml), the proliferative activity of Jurkat cells was significantly decreased, and a low and medium concentration of HMGB1 induced an up-regulation of p53 mRNA, p-p53 and p53 protein expression. Meanwhile, levels of mdm2 and p21 were elevated by incubated with HMGB1 (100 ng/ml) for 24 or 48 hours. Moreover, the proliferation of Jurkat cells in response to HMGB1 (100 ng/ml) in the vector group was significantly depressed. The bax and caspase-3 levels in p53 shRNA-expressed cells treated with HMGB1 (100 ng/ml) was markedly decreased, whereas expression of bcl-2 was obviously enhanced. Among ERK1/2, p38 MAPK and JNK1/2 signaling, only p38 MAPK pathway could be significantly activated by treatment with HMGB1, and the specific inhibitor of p38 MAPK was used, p53 and p-p53 expression induced by HMGB1 were significantly down-regulated. Taken together, our data strongly indicated that HMGB1 might enhance p53 expression, which was associated with both the proliferative activity as well as apoptosis of T cells.

[The preventive and therapeutic effect of advanced airway management on pulmonary infection in patients with inhalation injury after tracheotomy].

OBJECTIVE: To observe the preventive and therapeutic effect of advanced airway management on pulmonary infection in patients with inhalation injury after tracheotomy. METHODS: fourteen burn patients with inhalation injury admitted to our hospital from January 2001 to December 2004 were enrolled as control (C) group, and they were treated with conventional systemic therapy and management of airway. Twenty-seven burn patients with inhalation injury admitted to our hospital from January 2005 to October 2009 were enrolled as advanced (A) group, and they were treated with conventional systemic therapy and advanced airway management, including bedside isolation of airway, fixation of both oxygen supply tube and humidifying tube, humidification in specific body position, thinning of sputum, lavement of airway and procedural sputum elimination, steam inhalation combined with medicine, and suction of sputum with interrupted negative pressure. Result of bacterial culture of sputum (the 7th day after tracheotomy) and chest X-ray (at admission and the 7th day after tracheotomy), pulmonary infection, change in blood gas analysis index and oxygen saturation (SO(2)), (within 7 days after tracheotomy), and the number of patients curd in 2 groups were observed and compared. RESULTS: (1) Positive result of bacterial culture of sputum was observed in 11 (78.6%) patients in C group and 12 (44.4%) patients in A group. The difference between them was statistically significant (chi(2) = 4.36, P < 0.05). The main bacterium detected was Pseudomonas aeruginosa. (2) Pneumonia was suspected in 7 patients (25.9%) in A group by chest X-ray, which was obviously fewer than that in C group (8 Cases, 57.1%, chi(2) = 3.87, P < 0.05). The result was in accordance with the diagnosis of pulmonary infection. (3) No CO(2) retention, SO(2) and PaCO(2) abnormality caused by asphyxia was observed in 2 groups, PaCO(2) value in A group was close to that in C group (t = 0.89, P > 0.05). (4) In C group, 9 (64.3%) patients were cured, 5 patients died of pneumonia, wound sepsis, and MODS. In A group, 25 (92.6%) patients were cured, 2 patients died of MODS. Number of cure was obviously larger in A group than in C group (chi(2)= 5.22, P < 0.05). CONCLUSIONS: The advanced airway management has better effects on isolation and humidification of airway, and thinning, drainage, and elimination of sputum. And it can decrease the probability of blind suction and injury to airway, and it prevents pulmonary infection following tracheotomy.