PLZF⁺ Innate T Cells Support the TGF-β-Dependent Generation of Activated/Memory-Like Regulatory T Cells

Kang, Byung Hyun,Park, Hyo Jin,Park, Hi Jung,Lee, Jae-Il,Park, Seong Hoe,Jung, Kyeong Cheon Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.6

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether $PLZF^+$ innate T cells also affect the development and function of $Foxp3^+$ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant $PLZF^+$ CD4 T cells and invariant natural killer T cells, respectively, revealed that $Foxp3^+$ T cells in these mice exhibited a $CD103^+$ activated/memorylike phenotype. The frequency of $CD103^+$ regulatory T cells was considerably decreased in $PLZF^+$ cell-deficient $CIITA^{Tg}Plzf^{lu/lu}$ and $BALB/c.CD1d^{-/-}$ mice as well as in an IL-4-deficient background, such as in $CIITA^{Tg}IL-4^{-/-}$ and $BALB/c.IL-4^{-/-}$ mice, indicating that the acquisition of an activated/ memory-like phenotype was dependent on $PLZF^+$ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF-${\beta}$ enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/ memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of $CIITA^{Tg}PIV^{-/-}$ mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that $PLZF^+$ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

PLZF+ Innate T Cells Support the TGF-beta-Dependent Generation of Activated/Memory-Like Regulatory T Cells

Kyeong-Cheon Jung,Byung Hyun Kang,Hyo Jin Park,Hi Jung Park,Jae-il Lee,Seong Hoe Park 한국분자세포생물학회 2016 Molecules and cells Vol.39 No.6

PLZF-expressing invariant natural killer T cells and CD4 T cells are unique subsets of innate T cells. Both are selected via thymocyte-thymocyte interaction, and they contribute to the generation of activated/memory-like CD4 and CD8 T cells in the thymus via the production of IL-4. Here, we investigated whether PLZF+ innate T cells also affect the development and function of Foxp3+ regulatory CD4 T cells. Flow cytometry analysis of the thymus and spleen from both CIITA transgenic C57BL/6 and wild-type BALB/c mice, which have abundant PLZF+ CD4 T cells and invariant natural killer T cells, respectively, revealed that Foxp3+ T cells in these mice exhibited a CD103+ activated/memory-like phenotype. The frequency of CD103+ regulatory T cells was considerably decreased in PLZF+ cell-deficient CII-TATgPlzflu/lu and BALB/c.CD1d−/− mice as well as in an IL-4-deficient background, such as in CIITATgIL-4−/− and BALB/ c.IL-4−/− mice, indicating that the acquisition of an activated/memory-like phenotype was dependent on PLZF+ innate T cells and IL-4. Using fetal thymic organ culture, we further demonstrated that IL-4 in concert with TGF- enhanced the acquisition of the activated/memory-like phenotype of regulatory T cells. In functional aspects, the activated/memory-like phenotype of Treg cells was directly related to their suppressive function; regulatory T cells of CIITATgPIV-/- mice more efficiently suppressed ovalbumin-induced allergic airway inflammation compared with their counterparts from wild-type mice. All of these findings suggest that PLZF+ innate T cells also augmented the generation of activated/memory-like regulation via IL-4 production.

GM-CSF Promotes Antitumor Immunity by Inducing Th9 Cell Responses

Kim, Il-Kyu,Koh, Choong-Hyun,Jeon, Insu,Shin, Kwang-Soo,Kang, Tae-Seung,Bae, Eun-Ah,Seo, Hyungseok,Ko, Hyun-Ja,Kim, Byung-Seok,Chung, Yeonseok,Kang, Chang-Yuil American Association for Cancer Research 2019 Cancer immunology research Vol.7 No.3

<P>Granulocyte-macrophage colony-stimulating factor (GM-CSF) functions as an adjuvant for antitumor immunity through an unclear mechanism. By activating monocyte-derived dendritic cells, GM-CSF induces Th9 development and IL9 production, which facilitates antitumor cytotoxic T lymphocyte responses.</P><P>GM-CSF as an adjuvant has been shown to promote antitumor immunity in mice and humans; however, the underlying mechanism of GM-CSF–induced antitumor immunity remains incompletely understood. In this study, we demonstrate that GM-CSF potentiates the efficacy of cancer vaccines through IL9-producing Th (Th9) cells. GM-CSF selectively enhanced Th9 cell differentiation by regulating the COX2–PGE<SUB>2</SUB> pathway while inhibiting the differentiation of induced regulatory T (iTreg) cells <I>in vitro</I> and <I>in vivo</I>. GM-CSF–activated monocyte-derived dendritic cells converted tumor-specific nai¨ve Th cells into Th9 cells, and delayed tumor growth by inducing antitumor CTLs in an IL9-dependent manner. Our findings reveal a mechanism for the adjuvanticity of GM-CSF and provide a rationale for the use of GM-CSF in cancer vaccines.</P>

Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean AcupunctureMoxibustion Medicine Society 2005 대한침구의학회지 Vol.22 No.2

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

식육중 잔류항균물질 비교 조사 -서울지역 도축 소와 돼지를 중심으로-

변정옥 ( Jung Ok Byun ),강영일 ( Young Il Kang ),이달주 ( Dal Ju Lee ),황래홍 ( Lae Hong Hwang ),이양수 ( Yang Soo Lee ),이병동 ( Byung Dong Lee ) 한국가축위생학회 2002 韓國家畜衛生學會誌 Vol.25 No.3

This study was carried out to compare the residual antibiotic materials in muscles of slaughter cattle and swine from slaughterhouses in Seoul from 2000 to 2001 by EEC-4-plate method, Charm Il and HPLC method. 1. Residual antibiotic materials were detected from 95 samples(0.8%) by EEC-4-plate and 57 samples(10.2%) by Charm Il. The final HPLC method determined the positives are 43(45.3%) and 27(47.3%) respectively. 2. The detection ratios were 45% by EEC-4-plate and 47% by Charm Il. 3. Seventy samples were classified as tetracyclines 56(75.7.4%), sulfonamides 10(14.9%), β-lactam 6(8.1%) chloramphenicol 1(1.4%). Three of them were confirmed to be positive simmultaneously for tetracyclines, sulfonamides and chloramphenicol. 4. The highest residual concentration of chlortetracycline, oxytetracycline, sulfamethazine, sulfadimethoxine, sulfaquinoxaline, penicillin, ampicillin and chloramphenicol were 0.34, 11.29, 68.16, 0.13, 4.0, 0.12, 0.4 and 0.04ppm, respectively.

Effects of Aralia cordata Thunb. on Proteoglycan Release, Type II Collagen Degradation and Matrix Metalloproteinase Activity in Rabbit Articular Cartilage Explants

Baek, Yong-Hyeon,Seo, Byung-Kwan,Lee, Jae-Dong,Huh, Jeong-Eun,Yang, Ha-Ru,Cho, Eun-Mi,Choi, Do-Young,Kim, Deog-Yoon,Cho, Yoon-Je,Kim, Kang-Il,Park, Dong-Suk The Korean Acupuncture Moxibustion Medicine Societ 2005 대한침구의학회지 Vol.33 No.4

Background & Objective: Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracellular matrix. The purpose of this study was to investigate the effects of Aralia cordata Thunb. in inhibiting the release of glycosaminoglycan (GAG), the degradation of collagen, and MMP activity in rabbit articular cartilage explants. Methods : The cartilage-protective effects of Aralia cordata Thunb. were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMP activity, measurement of lactate dehydrogenase activity and histological analysis in rabbit cartilage explants culture. Results : Interleukin-la (IL-1a) rapidly induced GAG, but collagen was much less readily released from cartilage explants. Aralia cordata Thunb. significantly inhibited GAG and collagen release in a concentration-dependent manner. Aralia cordata Thunb. dose-dependently inhibited MMP-3 and MMP-13 expression and activities from IL-1a-treated cartilage explants cultures when tested at concentrations ranging from 0.02 to 0.2 mg/ml. Aralia cordata Thunb. had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Histological analysis indicated that Aralia cordata Thunb. reduced the degradation of the cartilage matrix compared with that of IL -1a-treated cartilage explants.

Effect of Cytokines and bFGF on the Osteoclast Differentiation Induced by 1α,25-(OH)<SUB>2</SUB>D<SUB>3</SUB> in Primary Murine Bone Marrow Cultures

Han-Jung Chae,Jang-Sook Kang,Byung-Gwan Bang,Seoung-Bum Cho,Jo-IL Han,Joo-Young Choi,Hyung-Min Kim,Soo-Wan Chae,Hyung Ryong Kim 대한생리학회-대한약리학회 1999 The Korean Journal of Physiology & Pharmacology Vol.3 No.6

<P> Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that IL-1β, IL-3, TNF-α, bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget s disease.

Activation of NKT Cells in an Anti-PD-1–Resistant Tumor Model Enhances Antitumor Immunity by Reinvigorating Exhausted CD8 T Cells

Bae, Eun-Ah,Seo, Hyungseok,Kim, Byung-Seok,Choi, Jeongwon,Jeon, Insu,Shin, Kwang-Soo,Koh, Choong-Hyun,Song, Boyeong,Kim, Il-Kyu,Min, Byung Soh,Han, Yoon Dae,Shin, Sang Joon,Kang, Chang-Yuil American Association for Cancer Research 2018 Cancer Research Vol.78 No.18

<P>These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer.</P><P>PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with cancer across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances antitumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of patients with cancer to anti-PD-1 therapy remains low, providing an urgent need for optimization and improvement. In this study, we designed an anti-PD-1–resistant mouse tumor model and showed that unresponsiveness to anti-PD-1 is associated with a gradual increase in CD8 T-cell exhaustion. We also found that invariant natural killer T cell stimulation by the synthetic ligand α-galactosylceramide (αGC) can enhance the antitumor effect in anti-PD-1–resistant tumors by restoring the effector function of tumor antigen–specific exhausted CD8 T cells. IL2 and IL12 were among the cytokines produced by αGC stimulation critical for reinvigorating exhausted CD8 T cells in tumor-bearing mice and patients with cancer. Furthermore, we observed a synergistic increase in the antitumor effect between αGC-loaded antigen-presenting cells and PD-1 blockade in a therapeutic murine tumor model. Our study suggests NKT cell stimulation as a promising therapeutic strategy for the treatment of patients with anti-PD-1–resistant cancer.</P><P><B>Significance:</B> These findings provide mechanistic insights into the application of NKT cell stimulation as a potent adjuvant for immunotherapy against advanced cancer. <I>Cancer Res; 78(18); 5315–26. ©2018 AACR</I>.</P>

<i>In vivo</i> genotoxicity evaluation of lung cells from Fischer 344 rats following 28 days of inhalation exposure to MWCNTs, plus 28 days and 90 days post-exposure

Kim, Jin Sik,Sung, Jae Hyuck,Choi, Byung Gil,Ryu, Hyeon Yeol,Song, Kyung Seuk,Shin, Jae Hoon,Lee, Jong Seong,Hwang, Joo Hwan,Lee, Ji Hyun,Lee, Gun Ho,Jeon, Kisoo,Ahn, Kang Ho,Yu, Il Je Informa Healthcare 2014 INHALATION TOXICOLOGY Vol. No.

<P>Despite their useful physico-chemical properties, carbon nanotubes (CNTs) continue to cause concern over occupational and human health due to their structural similarity to asbestos. Thus, to evaluate the toxic and genotoxic effect of multi-wall carbon nanotubes (MWCNTs) on lung cells <I>in vivo</I>, eight-week-old rats were divided into four groups (each group = 25 animals), a fresh air control (0 mg/m<SUP>3</SUP>), low (0.17 mg/m<SUP>3</SUP>), middle (0.49 mg/m<SUP>3</SUP>), and high (0.96 mg/m<SUP>3</SUP>) dose group, and exposed to MWCNTs <I>via</I> nose-only inhalation 6 h per day, 5 days per week for 28 days. The count median length and geometric standard deviation for the MWCNTs determined by TEM were 330.18 and 1.72 nm, respectively, and the MWCNT diameters ranged from 10 to 15 nm. Lung cells were isolated from five male and five female rats in each group on day 0, day 28 (only from males) and day 90 following the 28-day exposure. The total number of animals used was 15 male and 10 female rats for each concentration group. To determine the genotoxicity of the MWCNTs, a single cell gel electrophoresis assay (Comet assay) was conducted on the rat lung cells. As a result of the exposure, the olive tail moments were found to be significantly higher (<I>p</I> < 0.05) in the male and female rats from all the exposed groups when compared with the fresh air control. In addition, the high-dose exposed male and middle and high-dose exposed female rats retained DNA damage, even 90 days post-exposure (<I>p</I> < 0.05). To investigate the mode of genotoxicity, the intracellular reactive oxygen species (ROS) levels and inflammatory cytokine levels (TNF-α, TGF- β, IL-1, IL-2, IL-4, IL-5, IL-10, IL-12 and IFN-γ) were also measured. For the male rats, the H<SUB>2</SUB>O<SUB>2</SUB> levels were significantly higher in the middle (0 days post-exposure) and high- (0 days and 28 days post-exposure) dose groups (<I>p</I> < 0.05). Conversely, the female rats showed no changes in the H<SUB>2</SUB>O<SUB>2</SUB> levels. The inflammatory cytokine levels in the bronchoalveolar lavage (BAL) fluid did not show any statistically significant difference. Interestingly, the short-length MWCNTs deposited in the lung cells were persistent at 90 days post-exposure. Thus, exposing lung cells to MWCNTs with a short tube length may induce genotoxicity.</P>

특수교육기관의 직업교육 운영 내실화 방안

강병호,이유훈,김형일 국립특수교육원 2003 연구보고서 Vol.- No.4

장애학생이 '직업'을 갖고 산다는 것은 학교 졸업 이후에 가정으로 돌아 가는 것이 아니라 사회에서 '생산적인 활동'을 경험하며 의미 있게 시간을 보내는데 있어 매우 중요하며, 동시에 누군가에게 경제적으로 의존하지 않고 스스로 생활을 해결하는 발판이 되는 것이지만 우리 특수교육 현실은 장애 학생에게 적절한 직업교육이 이루어지지 않고 있으며, 그것이 가능하지 않은 구조라는 문제의식에서 '특수교육기관의 직업교육의 내실화 방안'을 강구해 보게 되었다. 특수교육기관의 장애학생 직업교육은 특수학교 및 특수학급의 교육과정에 중핵적인 비중을 차지하고 있음에도 불구하고 현재 특수학교의 초ㆍ중ㆍ고등부, 전공과와 초ㆍ중ㆍ고등학교 특수학급의 직업교육에 대한 교육과정 운영 실태, 운영 지원 체제의 실태에 대한 종합적인 분석자료가 미흡한 상황으로, 장애학생의 직업교육 운영에 대한 종합적인 실태조사를 통하여 그 현황과 문제점을 탐색하고 효율적인 내실화 운영 방안에 대한 종합적인 연구가 필요하였다. 이에 우리나라 특수학교 및 특수학급의 직업교육의 현황 및 문제점을 분석하고, 특수교육기관의 교사 및 장애학생 부모를 대상으로 장애학생 직업교육에 대한 실태 및 요구를 파악하여 특수교육기관의 장애학생 직업교육 및 훈련 체계를 확립하는 등 직업교육 운영의 내실화 방안을 마련하고자 했다. 본 연구를 통해 나타난 특수학교 직업교육의 가장 큰 문제는 직업교육 영역의 낙후성으로 현재 특수학교에서 실시하는 직업교과는 영역이 제한되어 현실적으로 취업 가능한 영역이라고 하기 어렵다는 것이며, 특수학급의 직업 교육에서 가장 큰 문제점은 특수학급에서 '직업'이라는 교육과정을 실시한다는 자체가 매우 어렵다는 것이었다. 또한 이러한 장애학생 직업교육의 문제점을 정확히 진단ㆍ개선하기 위해서는 장애학생의 직업평가ㆍ직업교육ㆍ취업알선 및 추수지도 등에 대한 지원체계를 분명히 확립해야 함을 분석할 수 있었다. 이에 특수교육기관의 직업교육 운영 내실화를 위해서, 장애영역별, 장애정도별, 학교(급)별, 초ㆍ중등 과정에 다른 다양한 직업교육체계를 구축, 진로 발달단계에 따른 적절한 직업교육 목표를 설정, 장애학생의 특성을 고려한 종합적인 진단ㆍ평가, 실무중심의 현실적인 직업교육내용 구축, 장애학생의 직업교육 시기에 따른 다양한 지원주체와 관련기관간의 연계체제 구축, 장애학생을 위한 다양한 직종개발, 가정과 학교의 연계제제 구축, 행ㆍ재정적인 지원을 확대해 나가야 할 것이다. 장애학생의 직업교육과 직업재활 및 전환을 위해서는 장애학생 직업재활 체계의 확립, 직업재활기관의 역할 분담, 직업재활기관의 다양화 및 직업교육 담당인력의 다원화 등을 모색하지 않으면 안될 것이다. 그러나 이러한 과제는 교육부분에서 뿐 만 아니라 장애인 직업재활 및 전환과 관련된 부처간ㆍ기관간 적극적인 협력을 요구한다는 사실을 잊지 말아야 할 것이다. 본 연구에서 제시한 방안들이 각 학교(급)의 실정에 맞게 재구성, 일반화 되어 직업교육 목표, 내용, 방법, 지원체제 및 지원여건 개선, 특수교육기관의 직업교육 운영개선으로 장애학생의 독립생활 촉진, 전국 특수교육기관의 균형적인 발전 도모와 장애학생 직업교육의 질 제고, 운영방안 및 정책 제언 등을 통해 장애학생 직업교육 성과 제고를 위한 합리적인 특수교육정책 수립의 기초자료 확보 등 장애학생 직업교육 체계를 확립하고 내실화를 기하는데 도움이 되기를 바라며 최종에는 장애학생의 학교교육 이후의 생활안정과 사회참여를 촉진하기 위한 지표가 될 것이다. Vocational education for the physically and mentally disabled students is given a great deal of weight in the curriculum of the special schools and the special classes in regular schools. But overall and analytic data are in short, which are pertaining to the actual conditions of operating the curriculum and the existing supporting system for it about the vocational education in the elementary, secondary, high special schools and in the special classes of the general elementary, secondary and high schools. Therefore, it is necessary that the synthetic research be done both to examine the real circumstances and problems and to seek the substantially effective methods of operating curricula through all-round investigation into the administration of the vocational education for the hanndicapped students. Hereupon I've made an analysis the circumstances and problems of the vocational education in the special schools and the special classes in our country, and got hold of and summed up their needs from teacher sand parents of the disabled students, so aimed at preparing the substantially effective methods in developing the system of the vocational education and offering vocatonal training for the disabled students of This research reveals that the most important problem of the vocational education in the special schools is, in one word, the backwardness of vocational education ; curriculum taught nowadays in the special schools are limited and not realistic enough to make one employed, above all, the education of 'vocation' itself in special classes is very hard to execute. And also this research shows that it is greatly needed the supporting system for the vocational evaluation, vocational education, agency of vocation and vocational guidance in order to precisely diagnose and improve the problems of the vocational education for the disabled students. Thereupon this study concludes that such programs as follows are urgent in order to serve the substantially effectiveness in performing the vocational education in the special educational institution : developing various educational systems for various vocations classified by the sphere of disabled, the informations of disabled, schools (classes), the elementary and the secondary grades; adjusting proper objectives of the vocational education based on the development steps in one's course; synthetic diagnose and evaluation of the disabled students considering their characteristics; building the contents of the vocational education with the actual practices; constructing close relationships between various supporting patrons and the authoritatives concerned on a basis of the stages of the vocational education; developing new various types of occupations for the disabled students; constructing closer relationships between the home and the school; extending the administrational and financial support. I heartily desire that substantial plan through this study should be restructured and generalized in accordance with the situations of each schools (classes) to help develop and substantialize the vocational education system for the disabled students in improving its purposes, contents, methods, supporting systems and supporting circumstances, and in the long run to help form a guideline for the disabled students to promote their social stability and social participation after graduation.