• IMMUNE NETWORK
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• v.14 no.1
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• pp.21-29
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• 2014

Follicular helper T ($T_{FH}$) cells are recently highlighted as their crucial role for humoral immunity to infection as well as their abnormal control to induce autoimmune disease. During an infection, na$\ddot{i}$ve T cells are differentiating into $T_{FH}$ cells which mediate memory B cells and long-lived plasma cells in germinal center (GC). $T_{FH}$ cells are characterized by their expression of master regulator, Bcl-6, and chemokine receptor, CXCR5, which are essential for the migration of T cells into the B cell follicle. Within the follicle, crosstalk occurs between B cells and $T_{FH}$ cells, leading to class switch recombination and affinity maturation. Various signaling molecules, including cytokines, surface molecules, and transcription factors are involved in $T_{FH}$ cell differentiation. IL-6 and IL-21 cytokine-mediated STAT signaling pathways, including STAT1 and STAT3, are crucial for inducing Bcl-6 expression and $T_{FH}$ cell differentiation. $T_{FH}$ cells express important surface molecules such as ICOS, PD-1, IL-21, BTLA, SAP and CD40L for mediating the interaction between T and B cells. Recently, two types of microRNA (miRNA) were found to be involved in the regulation of $T_{FH}$ cells. The miR-17-92 cluster induces Bcl-6 and $T_{FH}$ cell differentiation, whereas miR-10a negatively regulates Bcl-6 expression in T cells. In addition, follicular regulatory T ($T_{FR}$) cells are studied as thymus-derived $CXCR5^+PD-1^+Foxp3^+\;T_{reg}$ cells that play a significant role in limiting the GC response. Regulation of $T_{FH}$ cell differentiation and the GC reaction via miRNA and $T_{FR}$ cells could be important regulatory mechanisms for maintaining immune tolerance and preventing autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Here, we review recent studies on the various factors that affect $T_{FH}$ cell differentiation, and the role of $T_{FH}$ cells in autoimmune diseases.

• Journal of Periodontal and Implant Science
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• v.47 no.5
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• pp.292-311
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• 2017

Purpose: Beyond the limited scope of non-specific polyclonal regulatory T cell (Treg)-based immunotherapy, which depends largely on serendipity, the present study explored a target Treg subset appropriate for the delivery of a novel epitope spreader Pep19 antigen as part of a sophisticated form of immunotherapy with defined antigen specificity that induces immune tolerance. Methods: Human polyclonal $CD4^+CD25^+CD127^{lo-}$ Tregs (127-Tregs) and $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs (45RA-Tregs) were isolated and were stimulated with target peptide 19 (Pep19)-pulsed dendritic cells in a tolerogenic milieu followed by ex vivo expansion. Low-dose interleukin-2 (IL-2) and rapamycin were added to selectively exclude the outgrowth of contaminating effector T cells (Teffs). The following parameters were investigated in the expanded antigen-specific Tregs: the distinct expression of the immunosuppressive Treg marker Foxp3, epigenetic stability (demethylation in the Treg-specific demethylated region), the suppression of Teffs, expression of the homing receptors CD62L/CCR7, and CD95L-mediated apoptosis. The expanded Tregs were adoptively transferred into an $NOD/scid/IL-2R{\gamma}^{-/-}$ mouse model of collagen-induced arthritis. Results: Epitope-spreader Pep19 targeting by 45RA-Tregs led to an outstanding in vitro suppressive T cell fate characterized by robust ex vivo expansion, the salient expression of Foxp3, high epigenetic stability, enhanced T cell suppression, modest expression of CD62L/CCR7, and higher resistance to CD95L-mediated apoptosis. After adoptive transfer, the distinct fate of these T cells demonstrated a potent in vivo immunotherapeutic capability, as indicated by the complete elimination of footpad swelling, prolonged survival, minimal histopathological changes, and preferential localization of $CD4^+CD25^+$ Tregs at the articular joints in a mechanistic and orchestrated way. Conclusions: We propose human $na\ddot{i}ve$ $CD4^+CD25^+CD45RA^+$ Tregs and the epitope spreader Pep19 as cellular and molecular targets for a novel antigen-specific Treg-based vaccination against collagen-induced arthritis.

• Journal of Life Science
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• v.26 no.11
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• pp.1345-1354
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• 2016

Alopecia areata (AA) is a common and tissue-specific autoimmune disease of hair follicle resulting in the loss of hair on the scalp and elsewhere on the body. Hair follicles is a unique organ because it has its own immune system and hormonal milieu and has a different immune state at each hair cycle stage. The collapses of anagen-dependent hair follicle immune privilege arise autoimmune attack, inducing ectopic MHC class I expression in the hair follicle epithelium and autoantigen presentation to autoreactive CD8+T cells, which results in AA. Clinical and experimental studies have pointed that psychological stress may also influence the hair follicle immune/hormone systems and contribute to the induction of AA. The key pathogenesis of AA is associated with immune privilege guardians (including ACTH, ${\alpha}-MSH$, and $TGF-{\beta}$), natural killer group 2D-positive (NKG2D+) cells (including NK and CD8+T cells), and stress hormones (including CRH and substance P). Effective treatments for AA are still demanded. One of the future targets of treatment will be the modification of hair follicle immune privilege including stress. Recent studies have reported that JAK inhibitors and immunomodulators used in other autoimmune disease, such as psoriasis, atopic dermatitis, and rheumatoid arthritis, Tregs, platelet-rich plasma therapy, statins, and prostaglandin anaolgues are effective for AA. Here the article reviews the recent understanding in the pathogenesis associated with perifollicular endocrine/immunology and new treatments of AA.

• Journal of muscle and joint health
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• v.6 no.1
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• pp.100-135
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• 1999

Typical symptoms of rheumatic disease affect overall daily living and cause severe stress. Individuals afflicted with rheumatic disease have many illness-related stresses. Pain was the predominantly perceived stress followed by limitation in mobility, difficulties in carrying out activities of daily living. helplessness, dependency on others, threat to self-esteem, interference in social activity, interference in family relationships. difficulties performing at work, and discomfort of the treatment. Patients with chronic arthritis are subjected to long periods of continuous stress, which may require the management by the health care provider. In these cases, the purpose of the nursing is helping to promote health through supporting patient's coping. Therefore, for the nursing intervention to be effective, it is critical to build a theoretical framework that describes stress-coping for chronic arthritis. Thus, the purpose of this dissertation is to present a theoretical framework which describes the stress-coping processes and to empirically test pathos of this framework for the people with chronic arthritis. The foundation upon which this framework is built in the Erickson, Tomlin, and Swain(1983) theory of Modeling and role-Modeling. The subjects were 275 patients with rheumatoid arthritis or osteoarthritis who visited the outpatient clinic. A hypothetical model of stress-coping was tested by covariance structure analysis with PC-LISREL 8.12 program. As a result, the overall fit was good(Chi-square=94.49, P=0.00, RMR=0.067, GFI=0.95, AGFI=0.91, NNFI=0.93, NFI=0.91) for the hypothetical model. The results of hypothesis testing were as follows : Basic need satisfaction had a statistically significant influence on illness-related experience, emotional stress and coping resources. Internal health locus of control had a statistically significant influence on coping resources. However, independent variables(basic need satisfaction, internal health locus of control, illness-related experience, emotional stress and coping resource) did not have significantly influence on coping. And then, the hypothetical model was modified by considering both the theoretical implication and statistical significance of the parameter estimates. The revised model had a better fit to the data(Chi-square=83.11(P=0.00), RMR=0.061, GFI=0.96, AGFI=0.92, NNFI=0.95, NFI=0.92). Hypothesis emerged from the revised model was tested. The results of hypothesis testing were as follows : Basic need satisfaction had a statistically significant influence on illness-related experience, emotional stress and coping resources. Internal health locus of control had a statistically significant influence on illness-related experience and coping resources. Internal health locus of control, illness-related experience, emotional stress and coping resources had a significantly influence on coping. According to the results of this dissertation, basic need satisfaction and internal health locus of control play a central role in appraisal of illness-related experience and coping resources. And illness related-experience, emotional stress, and coping resources affect on coping activities. In summary, nursing interventions to enhance basic need satisfaction and internal health locus of control will decrease illness related experience and emotional stress and increase coping resources. Increased coping resources will prompt coping activities.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.233-238
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• 2002

Moxibustion is one of major healing technique in oriental medicine. It has been widely used in many diseases such as rheumatoid arthritis, Hashimoto disease, breech presentation, etc. However, till now, effects of moxibustion on NK cell activity and relations between sympathetic nerve system(SNS) and the immune alteration induced by moxibustion were not well studied. This study was designed to evaluate effects of moxibustion on NK cell activity and the intervention of SNS in the alteration of NK cell activity induced by moxibustion. Splenic NK cytotoxity was measured in a standard 4-h 51Cr release assay. We measured the NK cytotoxity at after moxibustion stimulation for 1,3,5, and 7 days, and also measured the NK cell cytotoxity after 3 and 7 days burn stimulation with similar temperature. IL-2, IL-4, INF-γ in serum were measured by rat IL-2, IL-4, INF-γ ELISA TEST KIT. To evaluate the effects of sympathectomy on alteration of NK cell cytotoxity, 6-hydroxydopamine(6-OHDA : 5Omg/kg) was used. We showed that NK cell activity of moxibustion stimulation group increased at the 3rd day, and declined at 7th day in comparison with that of contol group. In moxibustion stimulation group, NK cell activity of 3 day stimulation group was significantly higher than sham group. On the contrary, in burn stimulation group, NK cell activity was significantly higher than that of sham groups at 3rd, 7th days. Patterns between moxibustion and burns were different. INF- γ level of 3 days moxibustion stimulation group significantly higher than sham group. IL 2 level among groups were not different. IL-4 was not detected in serum with this method. Sympathectomy abolished the NK cell activity alteration induced by moxibustion. The results suggest that moxibustion induces the alteration of NK cell activity, along with INF-γ and SNS is related to these effects.

• Journal of Physiology & Pathology in Korean Medicine
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• v.21 no.5
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• pp.1278-1284
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• 2007

Solanum Iyratum Thunb (Solanaceae) has multiple applications in korean traditional medicine because of its cytotoxic, immunological and anti-inflammatory activities. However, no study on the anti-arthritic activity of Solanum Iyratum Thunb has been reported in vivo. Rheumatoid arthritis (RA) is a systemic autoimmune disease with chronic inflammation characterized by hyperplasia of synovial cells in affected joints, which ultimately leads to the destruction of cartilage and bone. Cytokine production were assessed during CIA(collagen-induced arthritis) model mice in lymph node (LN), in knee joint and spleen, using ELISA. DBA/1j mice were immunized with bovine type II collagen. After a second collagen immunization, mice were treated with Solanum Iyratum Thunb (SLT) orally at 400, 200 mg/kg once a day for 4 weeks. The severity of arthritis within the knee joints was evaluated by histological assessment of cartilage destruction and pannus formation. SLT significantly suppressed the progression of CIA and inhibited the production of TNF-alpha and IFN-gamma in serum and spleen cell culture supernatant. The erosion of cartilage was dramatically reduced in mouse knees after treatment with SLT. In conclusion, our results demonstrates that SLT significantly suppressed the progression of CIA. This action was characterized by suppression of arthritis index, cartilage erosion and synovial cell infiltration and the decreased production of $TNF-{\alpha}$, $IFN-{\gamma}$, CD4+, CD19+, CD3+/CD69+ cells (in lymph node), CD11b+/Gr-1 + (in knee joint).

• The Journal of Korean Physical Therapy
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• v.15 no.2
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• pp.131-145
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• 2003

The purpose of this study was to evaluate effects of artificial balenotherapy on the with degenerative osteoarthritis were selected as the subject do this study among the patients with degenerative osteoarthritis having pains in their knees by the criteria of America Rheumatoid Association. And the randomly selected ten patients out of the twenty were classified as an artificial balenotherapy group and the other the Patients were in a control group. Ten individuals with degenerative osteoarthritis patients in the artificial balenotherapy group Participated in artificial balenotherapy Program four weeks from March 1st, 2003 to March 31st, 2003 in Daegu 00 hospital. Ten individuals with degenerative osteoarthritis in the control group did not receive Artificial Balenotherapy. The conclusions were as follows: 1. After 4 weeks of therapy, the score of WBC(p < 0.01), RBC(p < 0.01), HTC(p < 0.01) in the artificial blalenotherapy group were significantly decreased, compared with their scores in pre-intervention. 2.In the balenotherapy group, significantly increase $Na^{+}$ ion(P < 0.05), decrease K ion(p < 0.01), unchanged Cl ion scores were found, compared with their scores in pro-intervention. 3. The result of the substudy about the effects of artificial balenotherapy on the substances that have relations with the function of liver were following that artificial balenotherapy group, increased total bilirubin(P < 0.01), unchanged total Protein, Albumin, total cholesterol, GOT, GPT, ALP were found, compared with their score in pre-intervention. 4. The result of the substudy about the effects of artificial balenotherapy on the substances that have relations with the function of kidney were following that in the artificial balenotherapy group, reduced BUN(P < 0.05), and increased creatine were found. 5. The result of the substudy about effects of artificial balenotherapy on the knee pain visual analog score, knee's functional score, ADL score were following that in the artificial balenotherapy group, decreased VAS score(P < 0.05), increased ADL score(p < 0.01), unchanged knee's functional score were founf, compared with their scores of the pre-intervention. In conclusion, the result of this study suggest that artificial balenotherapy improved ADL score and reduced knee pain visual analog score of the patients with degenerative osteoarthritis. The result proposed that appropriate use of artificial balenotherapy improves the degenerative osteoarthritis

• Journal of Pharmaceutical Investigation
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• v.31 no.2
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• pp.125-130
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• 2001

Bucillamine is a novel cysteine derivative with two free intramolecular sulfhydryl groups, and has a preventive and therapeutic effect on adjuvant arthritis, suggesting its antirheumatic action. With respect to the effect on the immune system, bucillamine-exerted such immunoregulating actions are to nomalize an excessive reduction or acceleration in immune reaction. It is useful not only in patients with early stage of rheumatoid arthritis (RA) but also in those with active RA retained for more than 10 years. The purpose of the present study was to evaluate the bioequivalence of two bucillamine tablets, $Rimatil^{TM}$ (Chong Kun Dang Pharmaceutical Co., Ltd.) and $Bucilin^{TM}$ (Kuhn Il Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.67{\pm}2.09$ years in age and $65.03{\pm}6.73\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After three tablets containing 100 mg of bucillamine per tablet were orally administered, blood was taken at predetermined time intervals and the concentrations of bucillamine in serum were determined using GC/MS with mass selective detector. Pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, $C_{max}\;and\;T_{max}$ between two tablets were -0.29%, -3.20% and 8.22%, respectively, when calculated against the $Rimatil^{TM}$ tablet. The powers $(1-{\beta})$ for $AUC_t\;and\;C_{max}$ were 84.31 % and 91.16%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.10$ and $1-{\beta}=0.8$ were less than 20% (e.g., 18.58% and 16.51% for $AUC_t\;and\;C_{max}$, respectively). The 90% confidence intervals were within ${\pm}20%$ (e.g.,$-12.77{\sim}12.20$ for $AUC_t$ and $-14.30{\sim}7.90$ for $C_{max}$). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Bucilin^{TM}$ tablet is bioequivalent to $Rimatil^{TM}$ tablet.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.501-508
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• 2014

BACKGROUND/OBJECTIVES: Rubus Coreanus Miquel (RCM), used as a traditional Korean medicine, reduces chronic inflammatory diseases such as cancer and rheumatoid arthritis. However, its mechanism has not been elucidated. In this study, we examine the anti-inflammatory effects of RCM and their possible mechanisms using RAW 264.7 cells. MATERIALS/METHODS: Unripe RCM ethanol extract (UE), unripe RCM water extract (UH), ripe RCM ethanol extract (RE), and ripe RCM water extract (RH) were prepared. Inflammatory response was induced with LPS treatment, and expression of pro-inflammatory mediators (iNOS, COX-2, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6) and NO and $PGE_2$ productions were assessed. To determine the anti-inflammatory mechanism of RCM, we measured NF-${\kappa}B$ and MAPK activities. RESULTS: UE and UH treatment significantly reduced NF-${\kappa}B$ activation and JNK and p38 phosphorylation and reduced transcriptional activities decreased iNOS, COX-2, and pro-inflammatory cytokines expressions, and NO and $PGE_2$ productions. RE and RH treatments reduced IL-$1{\beta}$ and IL-6 expressions through suppressions of JNK and p38 phosphorylation. CONCLUSIONS: In this study, we showed that RCM had anti-inflammatory effects by suppression of pro-inflammatory mediator expressions. Especially, unripe RCM showed strong anti-inflammatory effects through suppression of NF-${\kappa}B$ and MAPK activation. These findings suggest that unripe RCM might be used as a potential functional material to reduce chronic inflammatory responses.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.13 no.9
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• pp.4073-4081
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• 2012

This study was designed to estimate the prevalence of arthritis and to identify subgroups with high prevalence rates of arthritis. Study subjects were 18,406 Korean adults aged 19 and more from the 4th (2007-2009) Korea National Health and Nutrition Examination Surveys data. Annual self-reported prevalence and its rate ratios by demographic and behavioral factors were calculated using SAS 9.2 with survey procedure. The result was as follows. The crude prevalence of arthritis was 11.7% (osteoarthritis 10.2% and rheumatoid arthritis 1.7%). The prevalence was increased by age strata (2.4% in 19-44 aged, 16.4% in 45-64, 38.3% in 65 and more). After adjusting for age, we found the subgroups with high prevalence: older people, women, residents in non-apartment area, separated and divorced people, people with low education, people with several occupations (agricultural and fishery workers, elementary occupations, and unemployed), people with low household incomes, people with medical aid, and people with higher BMI. Those subgroups may be target populations in community health programs to control the disability from arthritis.