1.Leukocyte synapse: structure, function and significance.
Ke-Fu WU ; Guo-Guang ZHENG ; Xiao-Tong MA ; Yu-Hua SONG
Journal of Experimental Hematology 2010;18(4):829-833
Neuronal synapse is the critical structure of neuronal network. Immune system is mainly consisted of invisible network. Recently, evidence showed that leukocyte synapses between immune cells named as immunological synapses (IS), were formed under some functional conditions to form temporal local network. In fact, they are dynamic structures, which can be classified into synapse and kinase. Different leukocytes have different synapses. Inflammatory and leukemic cells showed special patterns of IS. Similar structure is also observed in some viral infected lymphocytes, which is called virological synapse (VS). This is one of the mechanisms for viral transmission, not only enhancing the transmission efficiency but also mediating the escape from antibody neutralization, leading persistent infection. Recently the flower-like poly synapses was reported by French scientists. This is a multi-tunneling nanotube flower-like structure on cell surface. We had observed this kind of structure in EB virus infected human leukemic cell line J6-2. In this paper, the structure and function of leukocyte synapses are reviewed combined with authors' own work. Their significance is discussed.
Humans
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Immunological Synapses
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immunology
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physiology
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Leukocytes
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cytology
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immunology
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physiology
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virology
2.Actin Engine in Immunological Synapse.
Indre PIRAGYTE ; Chang Duk JUN
Immune Network 2012;12(3):71-83
T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse.
Actin Cytoskeleton
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Actins
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Antigen-Presenting Cells
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Biophysics
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Immune System
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Immunological Synapses
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Microscopy
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T-Lymphocytes
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Ursidae
3.Activated Leukocyte Cell Adhesion Molecule Modulates Th2 Immune Response in Atopic Dermatitis
Mi Seon OH ; Jung Yeon HONG ; Mi Na KIM ; Eun Ji KWAK ; Soo Yeon KIM ; Eun Gyul KIM ; Kyung Eun LEE ; Yun Seon KIM ; Hye Mi JEE ; Seo Hyeong KIM ; In Suk SOL ; Chang Ook PARK ; Kyung Won KIM ; Myung Hyun SOHN
Allergy, Asthma & Immunology Research 2019;11(5):677-690
PURPOSE: Activated leukocyte cell adhesion molecule (ALCAM), a member of the immunoglobulin superfamily, is highly expressed on dendritic cells. ALCAM and its receptor CD6 are co-stimulatory molecules in the immunological synapse; their interaction is required for T cell activation. While atopic dermatitis (AD) is recognized as a T helper 2 (Th2)-mediated allergic disease, the role of ALCAM in its pathogenesis is unclear. METHODS: ALCAM levels were measured in the serum of AD patients and AD-induced murine model by ovalbumin treatment. We next investigated transepidermal water loss, clinical score, Th2-immune responses, skin barrier gene expression and T-cell activation using wild-type (WT) and ALCAM deficiency mice. An oxazolone-induced AD-like model was also established and analyzed using WT- and ALCAM-deficient mice. RESULTS: We found that serum ALCAM levels were elevated in pediatric AD patients as well as WT AD mice, whereas Th2-type cytokine production and AD symptoms were suppressed in ALCAM-deficient mice. In addition, CD4+ effector T-cell counts in murine skin and skin-draining lymph nodes were lower in ALCAM-deficient mice than in their WT counterparts. ALCAM deficiency was also linked to higher expression of skin barrier genes and number of lamellar bodies. CONCLUSIONS: These findings indicate that ALCAM may contribute to AD pathogenesis by meditating a Th2-dominant immune response and disrupting the barrier function of the skin.
Activated-Leukocyte Cell Adhesion Molecule
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Animals
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Dendritic Cells
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Dermatitis, Atopic
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Gene Expression
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Humans
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Immunoglobulins
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Immunological Synapses
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Lymph Nodes
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Mice
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Ovalbumin
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Skin
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T-Lymphocytes
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Water
4.Chimeric antigen receptor (CAR)-modified natural killer cell-based immunotherapy and immunological synapse formation in cancer and HIV.
Dongfang LIU ; Shuo TIAN ; Kai ZHANG ; Wei XIONG ; Ndongala Michel LUBAKI ; Zhiying CHEN ; Weidong HAN
Protein & Cell 2017;8(12):861-877
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells contribute to the body's immune defenses. Current chimeric antigen receptor (CAR)-modified T cell immunotherapy shows strong promise for treating various cancers and infectious diseases. Although CAR-modified NK cell immunotherapy is rapidly gaining attention, its clinical applications are mainly focused on preclinical investigations using the NK92 cell line. Despite recent advances in CAR-modified T cell immunotherapy, cost and severe toxicity have hindered its widespread use. To alleviate these disadvantages of CAR-modified T cell immunotherapy, additional cytotoxic cell-mediated immunotherapies are urgently needed. The unique biology of NK cells allows them to serve as a safe, effective, alternative immunotherapeutic strategy to CAR-modified T cells in the clinic. While the fundamental mechanisms underlying the cytotoxicity and side effects of CAR-modified T and NK cell immunotherapies remain poorly understood, the formation of the immunological synapse (IS) between CAR-modified T or NK cells and their susceptible target cells is known to be essential. The role of the IS in CAR T and NK cell immunotherapies will allow scientists to harness the power of CAR-modified T and NK cells to treat cancer and infectious diseases. In this review, we highlight the potential applications of CAR-modified NK cells to treat cancer and human immunodeficiency virus (HIV), and discuss the challenges and possible future directions of CAR-modified NK cell immunotherapy, as well as the importance of understanding the molecular mechanisms of CAR-modified T cell- or NK cell-mediated cytotoxicity and side effects, with a focus on the CAR-modified NK cell IS.
Animals
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HIV Infections
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immunology
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therapy
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HIV-1
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immunology
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Humans
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Immunity, Cellular
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Immunological Synapses
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Immunotherapy
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Killer Cells, Natural
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transplantation
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Neoplasms
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immunology
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therapy
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Receptors, Antigen, T-Cell
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genetics
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immunology
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Recombinant Fusion Proteins
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genetics
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immunology
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T-Lymphocytes
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immunology
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transplantation