• Maxillofacial Plastic and Reconstructive Surgery
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• v.20 no.2
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• pp.97-100
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• 1998

Systemic lupus erythematosus is a severe cutaneous-systemic disorder of unknown etiology, It is represented with erythematous patches on the face in a so-called butterfly distribution, and characteristically classified as an autoimmune disease with antinuclear antibodies. The autoimmune diseases such as systemic lupus erythematosus, $Sj{\ddot{o}}gren$ syndrome, rheumatoid arthritis have been associated with lymphoid malignancy - leukemia, malignant lymphoma - which could involve various organs(spleen, liver, brain, mediastinal lymph node, supraclavicular lymph node, inguinal lymph node, cervical lymph node etc.). Many authors have studied about the association of systemic lupus erythematosus and malignant lymphoma, but exact etiology is still unknown. A common viral etioloty for systemic lupus erythematosus has been suggested since virus-like particles have been found in the glomerular endothelium of patients with systemic lupus erythematosus. These oncogenic viruses may be responsible for the higher frequency of malignant lymphoma in patients with systemic lupus erythematosus. In the other theory, the causes of malignant lymphoma are the defect of immune system due to systemic lupus erythematosus and the long-term use of therapeutics for treatment of systemic lupus erythematosus. When the cellular immune system(delayed hypersensitivity) is impaired by immunosuppressive drugs, it is likely that the body is no longer able to recognize and reject malignant cells as they arise; they continue to grow and divide unhindered. The impairment of the cellular immune system may allow growth of oncogenic virus or the survival of neoplatic tissues. 47-year old female patient treated systemic lupus erythematosus with steroid and immunosuppressive drugs for 5 years visited to our hospital due to elevated mass on left upper anterior maxilla area. By performing biopsy, we diagnosed this lesion as malignant lymphoma and referred to oncologist for chemotherapy. So we report a case of malignant lymphoma due to systemic lupus erythematosus with review of literatures.

• IMMUNE NETWORK
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• v.14 no.3
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.

• Genomics & Informatics
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• v.16 no.4
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• pp.19.1-19.11
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• 2018

MicroRNAs (miRNAs), small non-coding RNAs, have been implicated in various diseases and cellular functions as microregulators of gene expression. Although the history of miRNA investigation in autoimmune $Sj{\ddot{o}}gren^{\prime}s$ syndrome (SjS) is fairly short, a substantial amount of data has already been accumulated. These findings clearly indicate potential clinical implications of miRNAs, such as autoantigen expression and autoantibody production, viral miRNAs regulating the calcium signaling pathway, and aberrant immune cell regulation and cytokine production. Research endeavors in the field are currently underway to select disease-specific diagnostic and prognostic biomarkers by utilizing different types of tissues or biological specimens of SjS patients. Various techniques for miRNA analysis with different stringencies have been applied, with the most recent one being next-generation sequencing. This review compiles and highlights differentially-expressed miRNAs in various samples collected from SjS patients and their potential implications in the pathogenesis of SjS. To facilitate the development of miRNA-targeted personalized therapy in the future, we urge more follow-up studies that confirm these findings and elucidate the immunopathological roles of differentially-expressed miRNAs. Furthermore, improved diagnostic criteria for the disease itself will minimize sampling errors in patient recruitment, preventing the generation of inconsistent data.

• Korean Circulation Journal
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• v.53 no.12
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• pp.795-810
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• 2023

Background and Objectives: Myocarditis is a potentially fatal disease, but curative treatments have not yet been established. Myocardial inflammation is an important pathogenesis of this disease, and immunosuppressants such as methylprednisolone and immunoglobulin have been used for treatment; however, the effectiveness needs to be improved. Thalidomide and dipeptidyl peptidase (DPP) 4 inhibitors were recently investigated regarding their immunomodulatory properties. This study aimed to test whether thalidomide or a DPP4 inhibitor (evogliptin) can improve the effectiveness of myocarditis treatment using a rat model of experimental autoimmune myocarditis (EAM). Methods: Rats with or without myocarditis were administered thalidomide at 100 mg/kg/day and DPP4 inhibitor at 10 mg/kg/day orally. Measurement of echocardiography, serum inflammatory cytokines, myocardial histopathological examination, and immunohistochemical staining for leukocytes, macrophages, CD4+ T cells, and cytoskeleton were performed after 3 weeks, and the fibrosis area was measured after 3 and 6 weeks. Results: Thalidomide and DPP4 inhibitor did not reduce the severity of myocarditis compared with the EAM without treatment rats by comparing the echocardiographic data, myocardial CD4⁺, macrophages, neutrophil infiltrations, and the heart weight/body weight ratio in 3 weeks. The levels of inflammatory cytokines were not lower in the thalidomide and DPP4 inhibitor-treated group than in the untreated group in 3 weeks. In 6 weeks, thalidomide and DPP4 inhibitors did not reduce the fibrosis area compared to untreated groups. Conclusions: Although thalidomide and the DPP4 inhibitor had an immunomodulatory effect and are used against inflammatory diseases, they did not ameliorate myocardial inflammation and fibrosis in this rat model of EAM.

• IMMUNE NETWORK
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• v.23 no.6
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• pp.46.1-46.16
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• 2023

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gamma-inducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.

• IMMUNE NETWORK
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• v.23 no.3
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• pp.29.1-29.23
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• 2023

Cholesterol (CL) is required for various biomolecular production processes, including those of cell membrane components. Therefore, to meet these needs, CL is converted into various derivatives. Among these derivatives is cholesterol sulfate (CS), a naturally produced CL derivative by the sulfotransferase family 2B1 (SULT2B1), which is widely present in human plasma. CS is involved in cell membrane stabilization, blood clotting, keratinocyte differentiation, and TCR nanocluster deformation. This study shows that treatment of T cells with CS resulted in the decreased surface expression of some surface T-cell proteins and reduced IL-2 release. Furthermore, T cells treated with CS significantly reduced lipid raft contents and membrane CLs. Surprisingly, using the electron microscope, we also observed that CS led to the disruption of T-cell microvilli, releasing small microvilli particles containing TCRs and other microvillar proteins. However, in vivo, T cells with CS showed aberrant migration to high endothelial venules and limited infiltrating splenic T-cell zones compared with the untreated T cells. Additionally, we observed significant alleviation of atopic dermatitis in mice injected with CS in the animal model. Based on these results, we conclude that CS is an immunosuppressive natural lipid that impairs TCR signaling by disrupting microvillar function in T cells, suggesting its usefulness as a therapeutic agent for alleviating T-cell-mediated hypersensitivity and a potential target for treating autoimmune diseases.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.36.1-36.13
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• 2020

Hippo signaling pathways are evolutionarily conserved signal transduction mechanisms mainly involved in organ size control, tissue regeneration, and tumor suppression. However, in mammals, the primary role of Hippo signaling seems to be regulation of immunity. As such, humans with null mutations in STK4 (mammalian homologue of Drosophila Hippo; also known as MST1) suffer from recurrent infections and autoimmune symptoms. Although dysregulated T cell homeostasis and functions have been identified in MST1-deficient human patients and mouse models, detailed cellular and molecular bases of the immune dysfunction remain to be elucidated. Although the canonical Hippo signaling pathway involves transcriptional co-activator Yes-associated protein (YAP) or transcriptional coactivator with PDZ motif (TAZ), the major Hippo downstream signaling pathways in T cells are YAP/TAZ-independent and they widely differ between T cell subsets. Here we will review Hippo signaling mechanisms in T cell immunity and describe their implications for immune defects found in MST1-deficient patients and animals. Further, we propose that mutual inhibition of Mst and Akt kinases and their opposing roles on the stability and function of forkhead box O and β-catenin may explain various immune defects discovered in mutant mice lacking Hippo signaling components. Understanding these diverse Hippo signaling pathways and their interplay with other evolutionarily-conserved signaling components in T cells may uncover molecular targets relevant to vaccination, autoimmune diseases, and cancer immunotherapies.

• Biotechnology and Bioprocess Engineering:BBE
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• v.7 no.3
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• pp.150-154
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• 2002

Monoclonal antibodies (Mabs) have been used as diagnostic and analytical reagents since hybridoma technology was invented in 1975. In recent years, antibodies have become increasingly accepted as therapeutics for human diseases, particularly for cancer, viral infection and autoimmune disorders. An indication of the emerging significance of antibody-based therapeutics is that over a third of the proteins currently undergoing clinical trials in the United States are antibodies. Until the late 1980's, antibody technology relied primarily on animal immunization and the expression of engineered antibodies. However, the development of methods for the expression of antibody fragments in bacteria and powerful techniques for screening combinatorial libraries, together with the accumulating structure-function data base of antibodies, have opened unlimited opportunities for the engineering of antibodies with tailor-made properties for specific applications. Antibodies of low immunogenicity, suitable for human therapy and in vivo diagnosis, can now be developed with relative ease. Here, antibody structure-function and antibody engineering technologies are described.

• Annals of Clinical Neurophysiology
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• v.10 no.2
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• pp.112-115
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• 2008

Colchicine is a drug used for the treatment of acute gouty arthritis or various autoimmune diseases. Gastrointestinal adverse effects such as abdominal pain and vomiting are the common side effects of the drug, but rarely myopathy has been reported to occur particularly in renal recipients who were treated concomitantly with immunosuppressants. Herein, we report a case who presented with acute myopathy after treated with colchicine for acute gouty arthritis.

• IMMUNE NETWORK
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• v.12 no.1
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• pp.1-7
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• 2012

Interleukin-24 (IL-24) belongs to the IL-10 family of cytokines and is well known for its tumor suppressor activity. This cytokine is released by both immune and nonimmune cells and acts on non-hematopoietic tissues such as skin, lung and reproductive tissues. Apart from its ubiquitous tumor suppressor function, IL-24 is also known to be involved in the immunopathology of autoimmune diseases like psoriasis and rheumatoid arthritis. Although the cellular sources and functions of IL-24 are being increasingly investigated, the molecular mechanisms of IL-24 gene expression at the levels of signal transduction, epigenetics and transcription factor binding are still unclear. Understanding the specific molecular events that regulate the production of IL-24 will help to answer the remaining questions that are important for the design of new strategies of immune intervention involving IL-24. Herein, we briefly review the signaling pathways and transcription factors that facilitate, induce, or repress production of this cytokine along with the cellular sources and functions of IL-24.