• IMMUNE NETWORK
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• v.24 no.2
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• pp.14.1-14.26
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• 2024

The inflammatory response during cutaneous leishmaniasis (CL) involves immune and non-immune cell cooperation to contain and eliminate Leishmania parasites. The orchestration of these responses is coordinated primarily by CD4⁺ T cells; however, the disease outcome depends on the Th cell predominant phenotype. Although Th1 and Th2 phenotypes are the most addressed as steers for the resolution or perpetuation of the disease, Th17 cell activities, especially IL-17 release, are recognized to be vital during CL development. Th17 cells perform vital functions during both acute and chronic phases of CL. Overall, Th17 cells induce the migration of phagocytes (neutrophils, macrophages) to the infection site and CD8⁺ T cells and NK cell activation. They also provoke granzyme and perforin secretion from CD8⁺ T cells, macrophage differentiation towards an M2 phenotype, and expansion of B and Treg cells. Likewise, immune cells from the inflammatory infiltrate have modulatory activities over Th17 cells involving their differentiation from naive CD4⁺ T cells and further expansion by generating a microenvironment rich in optimal cytokines such as IL-1β, TGF-β, IL-6, and IL-21. Th17 cell activities and synergies are crucial for the resistance of the infection during the early and acute stages; however, if unchecked, Th17 cells might lead to a chronic stage. This review discusses the synergies between Th17 cells and the inflammatory infiltrate and how these interactions might destine the course of CL.

• Parasites, Hosts and Diseases
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• v.57 no.3
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• pp.225-232
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• 2019

Innate lymphoid cells (ILCs) are key players during an immune response at the mucosal surfaces, such as lung, skin, and gastrointestinal tract. Giardia lamblia is an extracellular protozoan pathogen that inhabits the human small intestine. In this study, ILCs prepared from the lamina propria of mouse small intestine were incubated with G. lamblia trophozoites. Transcriptional changes in G. lamblia-exposed ILCs resulted in identification of activation of several immune pathways. Secretion of interleukin (IL)-17A, IL-17F, $IL-1{\beta}$, and interferon-${\gamma}$ was increased, whereas levels of IL-13, IL-5, and IL-22, was maintained or reduced upon exposure to G. lamblia. Goup 3 ILC (ILC3) was found to be dominant amongst the ILCs, and increased significantly upon co-cultivation with G. lamblia trophozoites. Oral inoculation of G. lamblia trophozoites into mice resulted in their presence in the small intestine, of which, the highest number of parasites was detected at the 5 days-post infection. Increased ILC3 was observed amongst the ILC population at the 5 days-post infection. These findings indicate that ILC3 from the lamina propria secretes IL-17 in response to G. lamblia, leading to the intestinal pathology observed in giardiasis.

• Journal of Preventive Veterinary Medicine
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• v.43 no.4
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• pp.214-220
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• 2019

Although canine brucellosis has been known to be an important re-emerging zoonosis, the pathophysiological mechanisms of Brucella canis infection remains clues to be solved. Different culture models, single and co-culture models, were constructed with canine epithelial cells, D17 and macrophage, DH82 to investigate the induction of immune responses in in vivo B. canis infection. Expression of genes related with induction of immune responses, Th1, Th2 and Th17, was compared in the two different models after the bacterial infection. In this study, expression of cytokine genes, IL-1β, IL-5, IL-6, IL-10, IL-23, and TNF-α was quantified in the DH82 at different time points using RT-qPCR in the two different culture systems after the infection. Cytokine genes related with Th1, IL-1β and TNF-α and Th17, IL-6 and IL-23 were expressed with time-dependent manners in the both systems (p<0.05). However, increase of Th2-related cytokine genes expression was not detectable in the both systems by comparison with control. The expression of Th1 and Th17 related cytokine genes was earlier in single cell culture than those in co-culture model (p<0.05). In general, amounts of the expressed genes were shown higher in single cell model than those in co-culture models. This study indicate that Th1 and Th17-associated immune responses are central to B. canis infection in dogs. In addition, it suggests a specific role of epithelial cells in the B. canis infection in vivo, which should resolved in the further study.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.5
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• pp.2389-2394
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• 2016

Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6, IL10 are known to influence the growth & survival of the malignant clone. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on the patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups. Survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients' survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1351-1355
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• 2016

Background: Multiple myeloma (MM) is influenced by genetic and micro-environmental changes. Malignant plasma cells produce an abnormal monoclonal immunoglobulin, as well as cytokines, such as IL-10 and IL-6 which stimulate cells of the bone marrow microenvironment (BMM) and cause dysfunction and failure of many organs. B cell activating factor (BAFF), IL6 and IL10 are known to influence the growth and survival of malignant clones. Aim: The objectives of the present study were to investigate the circulating levels of BAFF, IL-10 and IL-6, correlate them with well-known parameters of disease activity in patients with MM, and to detect their impact on patients' survival. Materials and Methods: This study was conducted on 89 newly diagnosed MM patients and seventy apparently healthy volunteers as a normal control group. BAFF, IL6, IL10 were measured by ELISA for both groups and survival analysis was performed for all patients. Results: Studied markers were higher in the MM patients compared to the normal control subjects. Patients survival was improved by high serum BAFF levels. Conclusions: High levels of BAFF were found to improve patients' survival. BAFF and IL-6 can be considered probable diagnostic markers for MM.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.71-76
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• 2015

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

• IMMUNE NETWORK
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• v.14 no.2
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• pp.89-99
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• 2014

Graft-versus-host disease (GVHD) is a fatal complication that occurs after allogeneic hematopoietic stem cell transplantation. To understand the dynamics of CD4 and CD8 T cell production of IFN-${\gamma}$ and IL-17 during GVHD progression, we established a GVHD model by transplanting T cell-depleted bone marrow (TCD-BM) and purified T cells from B6 mice into irradiated BALB.B, creating an MHC-matched but minor histocompatibility (H) antigen-mismatched transplantation (B6 ${\rightarrow}$ BALB.B GVHD). Transplantation-induced GVHD was confirmed by the presence of the appropriate compositional changes in the T cell compartments and innate immune cells in the blood and the systemic secretion of inflammatory cytokines. Using this B6 ${\rightarrow}$ BALB.B GVHD model, we showed that the production of IFN-${\gamma}$ and IL-17 by CD4 T cells preceded that by CD8 T cells in the spleen, mesenteric lymph node, liver, and lung in the BALB.B GVHD host, and Th1 differentiation predated Th17 differentiation in all organs during GVHD progression. Such changes in cytokine production were based on changes in cytokine gene expression by the T cells at different time points during GVHD development. These results demonstrate that both IFN-${\gamma}$ and IL-17 are produced by CD4 and CD8 T cells but with different kinetics during GVHD progression.

• International Journal of Oral Biology
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• v.42 no.1
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• pp.33-38
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• 2017

Background: Periodontitis is an inflammatory disease characterized by the breakdown of tooth-supporting tissues, leading to tooth loss. Aggregatibacter actinomycetemcomitans are major etiologic bacterium causing aggressive periodontitis. Ursodeoxycholic acid (UDCA), a hydrophilic gall bladder acid, has been used as an effective drug for various diseases related to immunity. The aim of this study was to investigate the effect of UDCA on the inflammatory response induced by A. actinomycetemcomitans. Methods: A human acute monocytic leukemia cell line (THP-1) was differentiated to macrophage- like cells by treatment with phorbol 12-mystristate 13-acetate (PMA) and used for all experiments. The cytotoxic effect of UDCA was examined by MTT assay. THP-1 cells were pretreated with UDCA for 30 min before A. actinomycetemcomitans infection and the culture supernatant was analyzed for various cytokine production by ELISA. The effect of UDCA on bacterial growth was examined by measuring optical densities using a spectrophotometer. Results: UDCA showed no cytotoxic effect on THP-1 cells, up to $80{\mu}M$ Ed highlight: Please confirm technical meaning. UDCA pretreatment inhibited the A. actinomycetemcomitans-induced $IL-1{\beta}$, $TNF-{\alpha}$, and IL-17A secretion in a dose-dependent manner. UDCA also inhibited IL-21 production at $60{\mu}M$. The production of IL-12 and IL-4 was not influenced by A. actinomycetemcomitans infection. Conclusion: These findings indicate that UDCA inhibits the production of inflammatory cytokines involved in innate and Th17 immune responses in A. actinomycetemcomitans-infected THP-1- derived macrophages, which suggests its possible use for the control of aggressive periodontitis.

• KSBB Journal
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• v.28 no.6
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• pp.415-422
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• 2013

Gamma irradiation (${\gamma}IR$) is widely used for radiotherapy as a treatment of cancer cells although it has a risk to damage normal cells. Inflammation is regarded as one of side effects of ${\gamma}IR$ while the effect of low dose of ${\gamma}IR$ on inflammation has not been researched well. Here, we investigated the inflammatory responses of low dose of ${\gamma}IR$ on murine spleen cells. It was evaluated if ${\gamma}IR$ affected the mitogen-induced lymphocyte proliferation, the regulation of various inflammatory cytokines (IFN-${\gamma}$, IL-2, IL-17, IL-4, IL-10), and the involvement of Ikaros and MAPK/NF-${\kappa}B$ medicated mechanism. Exposure of $^{137}Cs-{\gamma}IR$ below 2 Gy decreased the lymphocytes proliferative response to mitogens (LPS, ConA) except at the lowest dose, 0.05 Gy. IL-17, IL-2 and IL-4 mRNA increased at 0.5 and 2 Gy, but not altered at 0.05 Gy. IL-10, anti-inflammatory cytokine, increased only at 0.05 Gy. In regard to intracellular signaling, p-JNK, p-p38 and p-$I{\kappa}B{\alpha}$ were not changed, whereas the activation of ERK and Ikaros increased at the lowest dose. These results suggest that exposure of ${\gamma}IR$ less than 0.5 Gy (or below 0.05 Gy) has beneficial effects as a radiation hormesis on immune function.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3955-3960
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• 2012

Objective: To investigate the effects of $CD4^+$, IL17 and Foxp3 expression on prognosis of operable non-small cell lung cancer (NSCLC) with different pTNM stages. Methods: Expression of $CD4^+$, IL17 and Foxp3 in 102 cases of NSCLC tissues and adjacent cancer tissues was detected by immunohistochemistry and associations with prognosis with different pTNM stages were analyzed. The Chi-square test was used to compare count data. Survival differences were evaluated by Kaplan-Meier single factor analysis and the COX regression model was used to analyze the relationship between influential factors and the disease prognosis. The significance level was ${\alpha}$=0.05. Results: Expression of CD4, IL-17 and Foxp3 significantly varied in different pTNM stages of NSCLC tissues (P < 0.05). The same was true for CD4 expression (P < 0.05). The median survival time (MST) in the positive CD4 expression group was evidently higher than that in the negative group (25.8/23.9 months). Compared with stage III, the MST difference of stages I and II in the positive CD4 expression group were statistically significant (P < 0.05). The MST in positive IL-17 and Foxp3 expression groups was obviously lower than that in the corresponding negative group (P < 0.05) (25.6/35.1 months and 24/35.3 months, respectively). There was a significant difference of MST between any two of three stages of positive IL-17 expression group (P < 0.05), and it was the same with positive Foxp3 expression group. TNM stage, negative CD4 expression, and positive IL-17 and Foxp3 expression were the main risk factors for the prognosis of NSCLC. Conclusion: Surgical prognosis of NSCLC can be better assessed by the combination of clinical staging and expression of IL17 and Foxp3.