Summary Dedicator of cytokinesis 2 (Dock2), an atypical guanine exchange factor, is specifically expressed on immune cells and mediates cell adhesion and migration by activating Rac and regulates actin cytoskeleton remodeling. It plays a crucial role in the migration, formation of immune synapses, cell proliferation, activation of T and B lymphocytes and chemotaxis of pDCs and neutrophils. However, in‐vivo physiological functions of Dock2 have been relatively seldom studied. Our previous studies showed that Dock2−/− mice were highly susceptible to colitis induced by Citrobacter rodentium infection, and in early infection, Dock2−/− mice had defects in macrophage migration. However, the specific roles of Dock2 in the migration and functions of macrophages are not clear. In this study, we found that the expression of chemokines such as chemokine (C‐C motif) ligand (CCL)4 and CCL5 and chemokine receptors such as chemokine (C‐C motif) receptor (CCR)4 and CCR5 in bone marrow‐derived macrophages (BMDM) of Dock2−/− mice decreased after infection, which were supported by the in‐vivo infection experimental results; the Transwell experiment results showed that Dock2−/− BMDM had a defect in chemotaxis. The bacterial phagocytic and bactericidal experiment results also showed that Dock2−/− BMDM had the defects of bacterial phagocytosis and killing. Furthermore, the adoptive transfer of wild‐type BMDM alleviated the susceptibility of Dock2−/− mice to C. rodentium infection. Our results show that Dock2 affects migration and phagocytic and bactericidal ability of macrophages by regulating the expression of chemokines, chemokine receptors and their responses to chemokine stimulation, thus playing an essential role in the host defense against enteric bacterial infection.
Dedicator of cytokinesis 2 (DOCK2) can activate the downstream small G protein Rac and regulate cytoskeletal reorganization. DOCK2 is essential for critical physiological processes such as migration, activation, proliferation, and effects of immune cells, including lymphocytes, neutrophils, macrophages, and dendritic cells. For example, DOCK2 is involved in the development and activation of T and B lymphocytes by affecting synapse formation and inhibiting the development of the Th2 lineage by downregulating IL-4Rα surface expression. Not only that, DOCK2 may be a molecular target for controlling cardiac transplant rejection and Alzheimer’s disease (AD). Patients with defects in the DOCK2 gene also exhibit a variety of impaired cellular functions, such as chemotactic responses of lymphocytes and reactive oxygen species (ROS) production by neutrophils. To date, DOCK2 has been shown to be involved in the development of various diseases, including AD, pneumonia, myocarditis, colitis, tumors, etc. DOCK2 plays different roles in these diseases and the degree of inflammatory response has a different impact on the progression of disease. In this paper, we present a review of recent advances in the function of DOCK2 in various immune cells and its role in various diseases.
Human gastrointestinal cancer (e.g., gastric cancer and colorectal cancer) has been a leading cause of cancer-related deaths worldwide and has imposed a great threat to the public health. Although early-stage gastrointestinal cancer can be effectively treated by surgery, followed by postoperative chemotherapy, patients with advanced gastrointestinal cancer often exhibit poor prognosis and cancer relapse due to the absence of effective personalized treatment strategies. Patient-derived cancer organoid technology has been rapidly developed in recent years, and its emergence has opened up an unprecedented approach to model human cancers in vitro. Patient-derived cancer organoids involve the ex vivo culture of fragments of freshly resected human tumors that retain the histological features of original tumors. This review thoroughly discussed the evolutionary process of human gastrointestinal organoids cultured since 2009, and highlighted the potentials of patient-derived cancer organoids in clinical management of gastrointestinal cancer in terms of advances achieved in cancer modelling compared with conventional modelling methods, high-throughput drug screening, and development of personalized treatment selection. Additionally, the current limitations of patient-derived cancer organoids and the potential solutions to overcome these problems were summarized.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.