Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties. However, the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood. Here, our findings highlight the evolutionary continuity of RAB-10/Rab10's involvement in regulating innate immunity. Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa, an increase in RAB-10 activity was observed in the intestine. Conversely, when RAB-10 was absent, the intestinal diacylglycerols (DAGs) decreased, and the animal's response to the pathogen was impaired. Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector, facilitating the recruitment of phospholipase EGL-8 to endosomes. This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and an elevation of DAGs, as well as the activation of the PMK-1/p38 MAPK innate immune pathway. It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP) and the recruitment of EGL-8. Moreover, we ascertained that the rise in RAB-10 activity, due to infection, was attributed to the augmented expression of LET-413/Erbin, and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase. Hence, this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
Animals ; Caenorhabditis elegans/genetics* ; Endosomes/immunology* ; Caenorhabditis elegans Proteins/immunology* ; Phosphatidylinositol 4,5-Diphosphate/immunology* ; Immunity, Innate ; Pseudomonas aeruginosa/immunology* ; rab GTP-Binding Proteins/genetics* ; Diglycerides/metabolism*

Monoclonal antibodies have become the main type of antibody drug because of their high specificity and strong affinity to antigen. However, with the intensive study of the natural monoclonal antibody, many defects have faced, such as the limit times of binding to antigen, the unanticipated antibody clearance and antigen accumulation. Therefore, studies are no longer limited to the natural antibody screening, but rather to improve the efficiency of antibody drugs by engineering. In recent years, the bottlenecks in the development of conventional antibody have been solved effectively since the discovery of a novel recycling antibody. Recycling antibody binds to an antigen in plasma and dissociates from the antigen in endosome, thus maximizing the use of antibody and reducing antigen-mediated antibody clearance and antibody-mediated antigen accumulation. In addition, recycling antibodies can enhance the affinity with Fc receptors through further Fc modification. This paper reviews the research progress of circulating antibodies, including its characteristics, transformation methods and prospects.
Antibodies, Monoclonal ; immunology ; Antigens ; Endosomes ; Protein Binding ; Receptors, Fc

Exosomes are nanometer sized membrane vesicles, released in the extracellular milieu following the fusion of the external membrane of multivesicular body (MVB) with plasma membrane. They perform a certain function in immune regulation. Exosomes have been shown to be released by cells of hematopoietic and non-hematopoietic origin. Tumour-derived exosomes (TEX) exist in the supernatant of tumour cells, plasma and malignant effusions of tumour patients. They contain native candidate tumour associated antigen and are capable of transferring antigens to T lymphocytes, therefore efficiently promoting cytotoxic T lymphocyte (CTL) activation and producing antitumor immunity. However, recent evidence shows that tumor exosomes may induce immunologic tolerance and even activate immunosuppression which makes tumour escape from the immune surveillance of the host immune system. In addition, tumor exosomes may mediate a growth-promoting effect on tumor cells. These discrepancies are almost certainly due to differences in the phenotype of the exosomes.
Antigen-Presenting Cells ; immunology ; Antigens, Neoplasm ; immunology ; Cytoplasmic Vesicles ; immunology ; Endosomes ; immunology ; metabolism ; Exosomes ; immunology ; Humans ; Neoplasms ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Escape

The aim of this study was to investigate whether exosomes derived from K562 cells and human monocyte-derived dendritic cells (DCs) transfected with total RNA of K562 cells are capable of inducing antigen-specific cytotoxic T lymphocytes (CTL) responses in vitro. DCs were generated from peripheral blood mononuclear cells (PBMNC) of healthy volunteers in the presence of GM-CSF and IL-4, and then were transfected with K562 RNA by using DOTAP lipofection. Exosomes was extracted from the supernatant of DCs and K562 cells. The T cell were activated to be tumor specific CTL after DCs and exosomes were co-cultured with autologous T cells derived from healthy volunteers' PBMNC. The effect of CTL on K562 cells was detected by MTT assay. The results showed that treatment of T cells with exosomes derived from K562 cells or DCs transfected with total RNA of K562 cells could significantly promote their killing ability on K562 cells as compared with untreated T cells (P < 0.05). The killing ability of T cells treated with exosomes on K562 cells was stronger than on HL-60 cells (P < 0.05). It is concluded that the specific CTL immune response to leukemia cells can be induced by exosomes derived from K562 cells.
Dendritic Cells ; cytology ; immunology ; Endosomes ; immunology ; Exocytosis ; immunology ; Humans ; K562 Cells ; Monocytes ; cytology ; RNA, Neoplasm ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection