• Molecules and Cells
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• v.44 no.5
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• pp.342-355
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• 2021

The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

• Journal of Acupuncture Research
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• v.18 no.1
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• pp.100-112
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• 2001

Objective : The purpose of this study is to investigate the immunological effect of Ramulus Cinnamomum aqua-acupuncture on the cellular immune response in mice with LPS induced arthritis. Methods : All the BALB/C mice used in this study were bred and maintaned in our pathogen-free mouse colony and were 6wk of age at the start of the experiment. The experimental model of arthritis was induced by injeciton of 300${\mu}g$/kg LPS in mice knee joint. Ramulus Cinnamomum aqua-acupuncture was injected into Yangnungchon(Gb34) of mice 2daily for 14days. Immunohistochemical analysis was carried out to assess CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 expression in common iliac lymph nodes and synovial menbrane after stimulation with Ramulus Cinnamomum. Electron microscopy was carried out to assess change of synovial membrane. Ramulus Cinnamomum aqua-acupuncture stimulation group was compared to control group and non stimutated with aqua-acupuncture. Resutts : At day 14 post arthritis onset, Immunohistological studies using monoclonal antibodies showed that Ramulus Cinnamomum aqua-acupuncture goup had decreased expression of CD4+, CD8+, CD11b, IL-$1{\beta}$, IL-2R and CD106 at common illiac lymph nodes and synovial membrane compared with control group. Conclusions : Ramulus Cinnamomum aqua-acupuncture stimulation inhibited the development of cellular immunity to LPS-induced arthritis in mice. Thus, aqua-acupuncture stimulation may have preventive effects on autoimmune inflammatory joint diseases. The effects of AA on immune function and disease activity in patients with RA warrant further investigation.

• IMMUNE NETWORK
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• v.24 no.1
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• pp.6.1-6.17
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• 2024

The intricate role of innate type-2 cytokines in immune responses is increasingly acknowledged for its dual nature, encompassing both protective and pathogenic dimensions. Ranging from defense against parasitic infections to contributing to inflammatory diseases like asthma, fibrosis, and obesity, these cytokines intricately engage with various innate immune cells. This review meticulously explores the cellular origins of innate type-2 cytokines and their intricate interactions, shedding light on factors that amplify the innate type-2 response, including TSLP, IL-25, and IL-33. Recent advancements in therapeutic strategies, specifically the utilization of biologics targeting pivotal cytokines (IL-4, IL-5, and IL-13), are discussed, offering insights into both challenges and opportunities. Acknowledging the pivotal role of innate type-2 cytokines in orchestrating immune responses positions them as promising therapeutic targets. The evolving landscape of research and development in this field not only propels immunological knowledge forward but also holds the promise of more effective treatments in the future.

• Journal of Pharmacopuncture
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• v.20 no.2
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• pp.107-111
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• 2017

Objectives: Radiation is one of the most important sources of free radical (such as reactive oxygen species) production, which plays an essential role in the etiology of over hundred diseases. The aim of the study was to investigate some immune parameters and hematological indices in healthy workers of the Radiology Department, University Hospital of Mashhad, Iran. Methods: The study was performed on 50 healthy workers: 30 radiology staff as the case group and 20 laboratory workers as the control group. The radiation dose received by the radiology staff participating in the study was less than the annual maximum permissible level, 50 millisievert. Hematological parameters, lymphocyte proliferation and cytokine production were studied in both groups. Results: Among healthy radiology workers, the hematological indices did not differ statistically; however, their proliferation indices and $IFN-{\gamma}$ levels showed significant increases in parallel with decreases in the IL-4 levels as compared to controls. The immune system of workers exposed to low-dose ionizing radiation was found to be shifted from a Type 2 to a Type 1 response to promote cellular immunity. Conclusion: Based on our data, exposure to low-dose ionizing radiation may decrease the prevalence, frequency, and recurrence of various cancers and infectious diseases because of an increase in Th1-cell-based response, thus leading to more protection of the human body against tumor cells and foreign agents and possibly increased longevity. However, due to high rate of fluoroscopy use for interventional radiology, we suggest continuing research projects on radiation protection and hazards to prevent irreversible damage. As a recommendation, in future studies, radiology staff with a weakened immunity due to high radiation exposure should be considered as good choices to be treated using acupuncture techniques because acupuncture has been demonstrated to enhance the function and the number of immune cells.

• Korean Journal of Veterinary Research
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• v.34 no.2
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• pp.307-313
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• 1994

We have previously shown that crude water extract of Euonymus alatus (EA) had strong prophylactic effect against chemically induced-and tumor cell implanted-cancer, and that the mechanisms responsible for its antitumor effects were due to nonspecific enhancement of the NK cell activities and the cell mediated immunity. However, it was unknown that any components of crude extract did work so, since it consisted of several components. In this paper, we fractionated the crude watar EA-extract into several fraction such as hexane-, ethylether-, ethyl acetate-, n-butanol- and water soluble-fraction, and screened the immune regulating activities of each fraction by the evaluation of lymphokine production and activated lymphocyte proliferation. As a result of the component fraction of EA-extract, it was found that n-butanol fraction was a potent immunostimulator, and the remained water soluble fraction also contained some stimulator, But, other fraction did not showed any remarkable effect. It is therefore suggested that EA-glycosides in n-butanol fraction may be new one of the potent biological response modifiers. The present study was also undertaken in an efforts to investigate the effects of elm-bark(EB, Ulmus clavidiana var japonica), which has been used for curing ulcer and inflammation as a folk medicine without any kind of experimental evidence to support this, on the cellular- and humoral-immune responses, lymphocyte function and NK cell activities in mice. Regardless of time and duration of EB-treatment, Arthus reaction and antibody response to SRBC were not modified by EB, but delayed hypersensitivity to SRBC was significantly enhanced only when EB was treated prior to SRBC-sensitization. EB slightly inhibited the proliferation responses of splenocytes to PHA-stimulation, but it significantly augmented the responses of these cells to S aureus Cowan 1 and Con A-activation, and these effects were manifested only when EB was added at culture initiation. EB did not influence Ig secretion of spleen cells but it significantly augmented the Con A-induced 1L 2 and MIF production of splenocytes. NK cell activities of splenocytes were markedly riled when effector cells were pretreated with EB and this augmentation was dine to the increase of binding affinity of effector cells to target cells and the target cell lytic activities of effector cells. These results led to the conclusion that EB triggers increase of cellular immune responses, such as delayed hypersensitivitiy, lymphokine production and NK cell activities. Also these results suggested that EB contains potent immune stimulants, which may provide the rational basis for their therapeutic use as one of the new biological response modifiers.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.2
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• pp.108-115
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• 2003

Suppression of cellular immunity is the host responses to surgical stress. When the body is exposed to surgical stress, decreased immunocyte function is one of the surgical stress-induced biologic responses. In all patients exposed to the surgical stress, peripheral blood lymphocyte numbers and function were suppressed until at least 2 weeks postoperatively. This immunosuppression was mainly due to a decrease of helper-inducer T cells, cytotoxic T cells, natural killer cells, and an increase of suppressor T cells. The blood levels of interleukin-6(IL-6) cytokine increase in response to surgical stress and cause an increase of so-called acute phase reactants, including C-reactive protein(CRP). In the previously damaged patients group, expected to early stress expose, immunosuppression was more developed than other normal groups. Cellular immunosuppression by surgical stress was mainly due to an increase of lymphocyte subsets that depress cellular immunity coupled with a decrease of the subsets that promote it. Overproduction of CRP in response to surgical stress may play an important role in the development of immunosuppression.

• Journal of Life Science
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• v.33 no.3
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• pp.295-303
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• 2023

Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.

• Toxicological Research
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• v.6 no.1
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• pp.21-28
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• 1990

This study was undertaken to evaluate the immune responses to sheep red blood cell (SRBC) and potential anti-tumor effect of Bacillus Calmette-Guerin (BCG) in the mice bearing rumor induced by DMBA. The frequencies of tumor appearances were 62% in DMBA-treated mice and 14% in DMBA and BCG-treated group, respectively. Cellular immune response such as delayed-type hypersensitivity (DTH) to SRBCs, natural killer (NK) cell activity and antigen-binding cell (ABC) assay were decreased apparently in the tumor bearing mice compared to the normal controls. Humoral immune responses such as hemagglutinin (HA) and hemolysin (HE) were noted to be reduced in the tumor bearing mice, but the spleen index increased in tumor bearing mice. All the immunological parameters in the DMBA and BCG-group appeared to be higher than those of only DMBA-treated group. These results indicated that DMBA-induced tumor suppressed host immune responses. Also, they imply the idea that BCG enhanced the immune responses of tumor-bearing host and antitumor effects.

• Asian-Australasian Journal of Animal Sciences
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• v.18 no.3
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• pp.439-452
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• 2005

Zinc is ubiquitous in all living cells. Structural and catalytic properties of cellular enzymes are zinc dependent. Zinc deficiency leads to a variety of pathological abnormalities with immune impairment. It is an established fact that nutritional status contributes to overall immune response of individuals. Outcome of zinc deficiency on immune system is so drastic that it is difficult to conceive at the first instance. Zinc supplementation has been advocated to prevent diarrheal disease in children with poor nutritional status. The bioavailability of zinc depends upon its sources. Moreover it varies between monogastrics and ruminants. Controversy still prevails between inorganic and organic sources of zinc with respect to their superiority in bioavailability. Zinc exerts immunostimulatory effects in various laboratory and farm animals. Animals having congenital zinc deficiency diseases like A46 lethal trait usually die due to impairment of the immune system unless treated with zinc. The immune mechanism of zinc and its effect on animals and man are discussed. Zinc has been considered as extremely safe at higher therapeutic doses, but does not provide any beneficial effect but rather may cause immunosuppression. More recently, zinc has been prescribed for immunodeficient hosts, to modulate the immune system so that to a certain extent it can combat against opportunistic pathogens.

• IMMUNE NETWORK
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• v.14 no.6
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• pp.265-276
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• 2014

The interactions between B7 molecules and CD28-family receptors are crucial in the regulation of adaptive cellular immunity. In cancer, the aberrant expression of co-inhibitory B7 molecules has been attributed to reduced anti-tumor immunity and cancer immune evasion, prompting the development of cancer therapeutics that can restore T cell function. Murine tumor models have provided significant support for the targeting of multiple immune checkpoints involving CTLA-4, PD-1, ICOS, B7-H3 and B7-H4 during tumor growth, and clinical studies investigating the therapeutic effects of CTLA-4 and PD-1 blockade have shown exceptionally promising results in patients with advanced melanoma and other cancers. The expression pattern of co-inhibitory B7 ligands in the tumor microenvironment has also been largely correlated with poor patient prognosis, and recent evidence suggests that the presence of several B7 molecules may predict the responsiveness of immunotherapies that rely on pre-existing tumor-associated immune responses. While monotherapies blocking T cell co-inhibition have beneficial effects in reducing tumor burden, combinatorial immunotherapy targeting multiple immune checkpoints involved in various stages of the anti-tumor response has led to the most substantial impact on tumor reduction. In this review, we will examine the contributions of B7- and CD28-family members in the context of cancer development, and discuss the implications of current human findings in cancer immunotherapy.