• IMMUNE NETWORK
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• v.12 no.5
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• pp.176-180
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• 2012

Although the majority of research on CD137 has been directed to T cells, it is becoming clear that this molecule has distinct functions in other lineages of cells, including non-hematopoietic cells. In particular, emerging evidence suggests that the CD137-its ligand (CD137L) network involving immune cells and non-immune cells, directly or indirectly regulates inflammation in both positive and negative manners. Bidirectional signaling through both CD137 and CD137L is critical in the evolution of inflammation: 1) CD137L signaling plays an indispensible role in the activation and recruitment of neutrophils by inducing the production of proinflammatory cytokines and chemokines in hematopoietic and non-hematopoietic cells such as macrophages, endothelial cells and epithelial cells; 2) CD137 signaling in NK cells and T cells is required for their activation and can influence other cells participating in inflammation via either their production of proinflammatory cytokines or engagement of CD137L by their cell surface CD137: 3) CD137 signaling can suppress inflammation by controlling regulatory activities of dendritic cells and regulatory T cells. As recognition grows of the role of dysregulated CD137 or CD137L stimulation in inflammatory diseases, significant efforts will be needed to develop antagonists to CD137 or CD137L.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1731-1735
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• 2013

Objective: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis. Methods: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules. Results: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes. Conclusions: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.

• IMMUNE NETWORK
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• v.9 no.4
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• pp.122-126
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• 2009

Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

• IMMUNE NETWORK
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• v.14 no.4
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• pp.171-181
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• 2014

Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.479-484
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• 2015

NOD2 (nucleotide-binding and oligomerization domain 2) was initially reported as a susceptibility gene for Crohn's disease, with several studies focused on elucidating its molecular mechanism in the progression of Crohn's disease. We now know that NOD2 is an intracellular bacterial sensing receptor, and that MDP-mediated NOD2 activation drives inflammatory signaling. Various mutations in NOD2 have been reported, with NOD2 loss of function being associated with the development of Crohn's disease and other autoimmune diseases. These results suggest that NOD2 not only has an immune stimulatory function, but also an immune regulatory function. Atherosclerosis is a chronic inflammatory disease of the arterial wall; its pathologic progression is highly dependent on the immune balance. This immune balance is regulated by infiltrating monocytes and macrophages, both of which express NOD2. These findings indicate a potential role of NOD2 in atherosclerosis. The purpose of this review is to outline the known roles of NOD2 signaling in the pathogenesis of atherosclerosis.

• Journal of the Korean Institute of Intelligent Systems
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• v.11 no.7
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• pp.591-597
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• 2001

In this paper, we propose a method of cooperative control (T-cell modeling) and selection of group behavior strategy (B-cell modeling) based on immune system in distributed autonomous robotic system (DARS). Immune system is living body's self-protection and self-maintenance system. These features can be applied to decision making of optimal swarm behavior in dynamically changing environment. For applying immune system to DARS, a robot is regarded as a B-cell, each environmental condition as an antigen, a behavior strategy as an antibody and control parameter as a T-cell respectively. The executing process of proposed method is as follows. When the environmental condition changes, a robot selects an appropriate behavior strategy. And its behavior strategy is stimulated and suppressed by other robot using communication. Finally much stimulated strategy is adopted as a swarm behavior strategy. This control school is based on clonal selection and idiotopic network hypothesis. And it is used for decision making of optimal swarm strategy. By T-cell modeling, adaptation ability of robot is enhanced in dynamic environments.

• IMMUNE NETWORK
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• v.8 no.2
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• pp.46-52
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• 2008

Background: Oral tolerance is defined by the inhibition of immune responsiveness to a protein previously exposed via the oral route. Protein antigens exposed via the oral route can be absorbed through the mucosal surfaces of the gastrointestinal tract and can make physical contact with immune cells residing in the intestinal lamina propria (LP). However, the mechanisms of oral tolerance and immune regulation in the intestines currently remain to be clearly elucidated. Methods: In order to determine the effect of oral protein antigen intake (ovalbumin, OVA) on the intestinal LP, we assessed the expression profile of the T cell receptor and the co-receptors on the cells from the intestines of the tolerant and immune mouse groups. Results: We determined that the proportion of OVA-specific B cells and ${\gamma}{\delta}$ T cells had decreased, but the CD8${\alpha}{\beta}$ and D8${\alpha}{\alpha}$ T cells were increased in the LP from the tolerant group. The proportion of CD8＋ T cells in the spleen did not evidence any significant differences between treatment groups. Conclusion: These results indicate that CD8＋ T cells in the intestinal LP may perform a regulatory role following antigen challenge via the oral route.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.249-256
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• 2013

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

• Clinical and Experimental Reproductive Medicine
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• v.38 no.3
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• pp.119-125
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• 2011

Implantation of an embryo occurs during the mid-secretory phase of the menstrual cycle, known as the "implantation window." During this implantation period, there are significant morphologic and functional changes in the endometrium, which is followed by decidualization. Many immune cells, such as dendritic and natural killer (NK) cells, increase in number in this period and early pregnancy. Recent works have revealed that antigen-presenting cells (APCs) and NK cells are involved in vascular remodeling of spiral arteries in the decidua and lack of APCs leads to failure of pregnancy. Paternal and fetal antigens may play a role in the induction of immune tolerance during pregnancy. A balance between effectors (i.e., innate immunity and helper T [Th] 1 and Th17 immunity) and regulators (Th2 cells, regulatory T cells, etc.) is essential for establishment and maintenance of pregnancy. The highly complicated endocrine-immune network works in decidualization of the endometrium and at the fetomaternal interface. We will discuss the role of immune cells in the implantation period and during early pregnancy.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.406-411
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• 2011

Background: Invariant Natural killer T (iNKT) cells, a distinct subset of CD1d-restricted T cells with invariant $V{\alpha}{\beta}$ TCR, functionally bridge innate and adaptive immunity. While iNKT cells share features with conventional T cells in some functional aspects, they simultaneously produce large amount of Th1 and Th2 cytokines upon T-cell receptor (TCR) ligation. However, gene expression pattern in two types of cells has not been well characterized. Methods: we performed comparative microarray analyses of gene expression in murine iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells by using Gene Set Enrichment Analysis (GSEA) method. Results: Here, we describe profound differences in gene expression pattern between iNKT cells and conventional $CD4^+CD25^-$ ${\gamma}{\delta}TCR^-$ T cells. Conclusion: Our results provide new insights into the functional competence of iNKT cells and a better understanding of their various roles during immune responses.