A positive feedback loop of IL-21 signaling provoked by homeostatic CD4+CD25- T cell expansion is essential for the development of arthritis in autoimmune K/BxN mice.

Jang, Eunkyeong,Cho, Sin-Hye,Park, Hyunjoo,Paik, Doo-Jin,Kim, Jung Mogg,Youn, Jeehee Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.8

<P>Rheumatoid arthritis is a joint-specific autoimmune inflammatory disease of unknown etiology. The K/BxN mouse is a model of rheumatoid arthritis that is thought to be mainly due to autoantibody-mediated inflammatory responses. We showed previously that homeostatic proliferation of autoreactive CD4(+) T cells is required for disease initiation in the K/BxN mice. In this study, we show that the homeostatically proliferating CD4(+)CD25(-) T cells produce IL-21. We generated IL-21R-deficient (IL-21R(-/-)) K/BxN mice and found that these mice were completely refractory to the development of spontaneous arthritis. They contained fewer CD4(+) T cells with a reduced proportion of homeostatically proliferating cells, fewer follicular Th cells, and, surprisingly, more Th17 cells than their control counterparts. They also failed to develop IgG1(+) memory B cells and autoantigen-specific IgG1 Ab-secreting cells. IL-21 induced expression of receptor activator of NF-kappaB ligand (RANKL) a regulator of osteoclastogenesis, and few RANKL-expressing infiltrates were found in the synovia of IL-21R(-/-) K/BxN mice. Thus, our results demonstrate that IL-21 forms a positive feedback autocrine loop involving homeostatically activated CD4(+) cells and that it plays an essential role in the development of autoimmune arthritis by mechanisms dependent on follicular Th cell development, autoreactive B cell maturation, and RANKL induction but independent of Th17 cell function. Consistent with this, in vivo administration of soluble the IL-21R-Fc fusion protein delayed the onset and progression of arthritis. Our findings suggest that effective targeting of IL-21-mediated processes may be useful in treating autoimmune arthritis.</P>

Splenic Long-Lived Plasma Cells Promote the Development of Follicular Helper T Cells during Autoimmune Responses

Jang, Eunkyeong,Cho, Wang Sik,Oh, Yeon-Kyung,Cho, Mi-La,Kim, Jung Mogg,Paik, Doo-Jin,Youn, Jeehee The American Association of Immunologists, Inc. 2016 JOURNAL OF IMMUNOLOGY Vol.196 No.3

<P>Long-lived plasma cells (LLPCs) develop under the help of follicular helper T (Tfh) cells and reside mainly in the bone marrow. However, these cells are unusually abundant in the spleen of several autoimmune models including K/BxNsf mice, yet their pathogenic impact remains unknown. To investigate a previously unappreciated role of splenic LLPCs, we sorted splenic plasma cells (PCs) from K/BxNsf and K/BxN mice, corresponding to LLPCs and conventional short-lived PCs, respectively, and compared their phenotypes and ability to prime and induce the differentiation of naive CD4(+) T cells into effector cells in vitro and in vivo. We found that K/BxNsf PCs had lower levels of the Ag presentation machinery and costimulators than K/BxN PCs, and also a lower CD4(+) T cell priming capacity. Autoantigen-pulsed K/BxNsf PCs selectively polarized cognate CD4(+) T cells toward the expression of molecules necessary for Tfh development and function. As a result, the K/BxNsf PC-primed CD4(+) T cells were more effective in stimulating B cells to produce autoantigen-specific IgGs than K/BxN PCs or even dendritic cells. Adoptive transfer of K/BxNsf PCs, but not K/BxN PCs, to K/BxN mice increased numbers of Tfh cells in draining lymph nodes. These results propose that abnormal accumulation of LLPCs in the spleen of autoimmune models drives the differentiation of autoantigen-primed CD4(+) T cells to Tfh cells. This positive feedback loop between splenic LLPCs and Tfh cells may contribute to the persistence of humoral autoimmunity.</P>

Centrality Degree, Opinion Leadership, and WOM of Nodes in Social Network Sites

DeKui Li,ByungKook Ha,JeeHee Cho 한국경영정보학회 2011 한국경영정보학회 학술대회논문집 Vol.2011 No.1

The WOM (Word-of-Mouth) is uncertain and uncontrollable, so marketers' interest turns to managing personal network in hope of managing WOM. In this regard, opinion leadership and social network analysis have become pivotal issues of WOM management. Central nodes, members having direct contacts with a great number of other members, play an important role in the WOM transmission as they can widely circulate information. Centrality degree, the counting of contacts of a node, is a sociometric technique used as a proxy for opinion leadership in lieu of a self-report method. In this paper, we have two purposes. First, we introduce two variables, centrality degree and prominence degree to jointly identify the true opinion leaders. While the centrality degree indicates the coverage capacity of opinion leaders, the prominence degree signifies the quality that the observed individuals' ideas and opinions are sought. Second, we attempt to reveal the behavior of opinion leaders regarding the WOM diffusion in that they generate as much NWOM as PWOM, as an evident of their unbiased opinion provisions.

Clonal Expansion of Type Ⅱ Collagen-reactive T-cells Expressing Conserved CDR3 Motifs in Korean Patients with Rheumatoid Arthritis

Kim, Seung-Hoon,Cho, Mi-La,Hwang, Sung-Hee,Youn, Jeehee,Park, Sung-Hwan,Hwang, Sue-Yun,Kim, Ho-Youn 가톨릭 의과학연구원 2001 가톨릭 의과학연구원 국제학술대회 Vol.5 No.-

A Survey of Prevention of Drowning Accidents in Korea

Marten Brienen,Byungjun Cho,Taeyoung Moon,Jeehee Kim,Jinwoo Kim 한국콘텐츠학회 2015 한국콘텐츠학회 종합학술대회 논문집 Vol.2015 No.5

Interleukin‐21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen‐induced arthritis

Kwok, Seung‐,Ki,Cho, Mi‐,La,Park, Mi‐,Kyung,Oh, Hye‐,Joa,Park, Jin‐,Sil,Her, Yang‐,Mi,Lee, Seon‐,Yeong,Youn, Jeehee,Ju, Ji Hyeon,Park, Kyung Su,Kim, Sung Wiley Subscription Services, Inc., A Wiley Company 2012 Vol.64 No.3

<P><B>Abstract</B></P><P><B>Objective</B></P><P>Bone destruction is a critical pathology involved in the functional disability caused by rheumatoid arthritis (RA). Osteoclasts, which are specialized bone‐resorbing cells regulated by cytokines such as RANKL, are implicated in bone destruction in RA. The aim of this study was to determine whether interleukin‐21 (IL‐21), a potent immunomodulatory 4–α‐helical bundle type 1 cytokine, has osteoclastogenic activity in patients with RA and in mice with collagen‐induced arthritis (CIA).</P><P><B>Methods</B></P><P>The expression of IL‐21 in synovial tissue was examined using immunohistochemistry. The concentrations of IL‐21 in serum and synovial fluid were determined by enzyme‐linked immunosorbent assay. The levels of RANKL and osteoclastogenic markers were measured using real‐time polymerase chain reaction. CD14+ monocytes from patients with RA or mouse bone marrow cells were cocultured with fibroblast‐like synoviocytes (FLS) from patients with RA or CD4+ T cells from mice with CIA in the presence of IL‐21 and subsequently stained for tartrate‐resistant acid phosphatase activity to determine osteoclast formation.</P><P><B>Results</B></P><P>IL‐21 was up‐regulated in the synovium, synovial fluid, and serum of patients with RA and in the synovium and serum of mice with CIA. IL‐21 induced RANKL expression in mixed joint cells and CD4+ T cells from mice with CIA and in CD4+ T cells and FLS from patients with RA. Moreover, IL‐21 enhanced in vitro osteoclastogenesis without the presence of RANKL‐providing cells and by inducing RANKL expression in CD4+ T cells and FLS.</P><P><B>Conclusion</B></P><P>Our data suggest that IL‐21 promotes osteoclastogenesis in RA. We believe that therapeutic strategies targeting IL‐21 might be effective for the treatment of patients with RA, especially in preventing bone destruction.</P>

류마티스관절염 환자로부터 분리한 윤활막섬유모세포의 TRALL에 대한 세포사멸 반응 및 TRAIL 수용체 발현 양상에 대한 조사

조원길(Won-Gil Cho),임현성(Hyun-Sung Leem),백두진(Doo-Jin Paik),정호삼(Ho-Sam Chung),김원규(Won-Kyu Kim),최충혁(Chung-Hyuk Choil),윤지희(Jeehee Youn) 대한체질인류학회 2001 해부·생물인류학 (Anat Biol Anthropol) Vol.14 No.3

류마티스관절염은 염증성 자가면역 질환의 일종으로 윤활막이 증식(hyperplasia)되는 소견을 나타내며, 이는 일부 형질전환된 특성을 지닌 윤활막세포에서 apoptosis의 장애가 일어나는 경과로 알려졌다. TNF-related apoptosis inducing ligand (TRAIL)은 TNF ligand superfamily의 일원으로, 두 수용체(TRAILR-l과 2)를 통해 세포사영 신호를 세포 내로 전달한다. 반면 두 decoy 수용체인 TRAILR-3와 4는 TRAIL 유도 세포사멸 경로를 방해한다. 류마티스관절염 판자의 윤활악서 1 포가 TRAIL 에 의하여 세포사영 반응이 일어나는지 조사하기 위하 여, 각각 두 명의 류마티스관절염 환자와 골관정염 환자로부터 분리 애양한 윤활약섬유오세포주들은 human TRAIL호 자극한 후 Mteassay를 실행하였다. 두 류마티스관정염 세포들은 TRAIL 에 반응하여 세포 생존융이 강소한 반면 , 골관정염 세포들은 TRAIL에 우반응을 보이거나 류마티스관정엽 세포에 비해 현저히 감소된 민강 성율 보였다 RT-PCT 과 연역조직화학적 분켜 결과 , TRAILR-I, -2 , -3의 발현 양상은 모든 세포주에서 유사했 으나 , TARILR-4 의 발현 정도는 류마티스 관절엽 세포에서 골판절엽 세포에 비해 강소한 경과를 보였다 그러므로, 이상의 결과들은 윤활막섬유모세포는 류마티스관절염 진행 과정 중 TRAIL을 통한 세포사멸에 대하여 민감성을 획득하며, 이런 세포사멸 신호는 TRAILR-4 발현의 조정에 일부 의존적일 것 2. 로 추정된다

Poly-γ-glutamic acid suppresses osteoclastogenesis in human osteoclast precursors and prevents joint damage in a collagen-induced murine arthritis model

Lee, Bitnara,Jo, Sungsin,Kim, Sung-Min,Cho, Mi-La,Park, Sung-Hwan,Youn, Jeehee,Ji, Jong Dae,Kim, Tae-Hwan Elsevier 2018 IMMUNOLOGY LETTERS Vol.203 No.-

<P><B>Abstract</B></P> <P>Poly–γ-glutamic acid (γ-PGA), a natural polymer derived from <I>Bacillus subtilis</I>, shows anti-inflammatory activity. However, the effects of γ-PGA on osteoclasts, which are important cells for joint destruction in inflammatory diseases such as rheumatoid arthritis (RA), have not yet been reported. In this study, we show that γ-PGA markedly inhibits osteoclast differentiation in normal PBMC-derived osteoclast precursors and in synovial fluid macrophages of patients with RA. γ-PGA also reduces RANK expression by down-regulating M-CSF receptors. Additionally, oral administration of γ-PGA attenuated bone destruction in a collagen-induced arthritis (CIA) model, demonstrating decreases in inflammation, cartilage damage, and osteoclast formation in histological analyses. Taken together, these data suggest that γ-PGA could be a good candidate for therapeutic prevention of joint destruction in RA.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Poly-γ-glutamic acid (γ-PGA) inhibited osteoclast differentiation in normal PBMC-derived osteoclast precursors and RA synovial fluid macrophages. </LI> <LI> Treatment with γ-PGA suppressed osteoclastogenesis <I>in vitro</I> and <I>in vivo</I>. </LI> <LI> Oral administration of γ-PGA markedly reduced bone destruction in collagen-induced mouse (CIA) model. </LI> </UL> </P>

Prevention of spontaneous arthritis by inhibiting homeostatic expansion of autoreactive CD4+ T cells in the K/BxN mouse model

Jang, Eunkyeong,Kim, Hong Ro,Cho, Sin Hye,Paik, Doo-Jin,Kim, Jung Mogg,Lee, Sang-Koo,Youn, Jeehee Wiley Subscription Services, Inc., A Wiley Company 2006 Vol.54 No.2

<B>Objective</B><P>K/BxN-transgenic mice are a model of autoimmune arthritis, similar to rheumatoid arthritis. This study was undertaken to determine whether inhibition of lymphopenia-provoked homeostatic expansion can prevent spontaneous development of disease in the K/BxN model.</P><B>Methods</B><P>To inhibit homeostatic expansion of autoreactive T cells, K/BxN mice with disease in the preclinical stage were adoptively transferred with CD4+ T cells purified from nontransgenic BxN or Thy1.1+ BxN mice. To observe the profile of proliferation of CD4+ T cells derived from the hosts, carboxyfluorescein diacetate succinimidyl ester–labeled autologous CD4+ T cells were cotransferred to K/BxN mice together with BxN CD4+ T cells. Disease onset and progression were scored, and the dynamics and phenotypes of recipient CD4+ T cells were determined by flow cytometry, before and after cell infusion.</P><B>Results</B><P>During the preclinical phase of disease, K/BxN mice exhibited CD4+ T lymphopenia, which was followed by a compensatory expansion of these cells during the early clinical phase. The majority of CD4+ T cells acquired a memory phenotype (CD44<SUP>high</SUP>,CD62L<SUP>low</SUP>,CD25−), which is a hallmark of homeostatically expanding cells. Importantly, K/BxN mice subjected to syngeneic T cell transfer did not develop symptoms of arthritis and also possessed fewer transgenic T cell receptor–encoded V<SUB>β</SUB>6+,CD4+ T cells. This effect was associated with decreased proliferation of recipient-derived CD4+ T cells but not with the function of CD25+ T regulatory cells present in donor cells.</P><B>Conclusion</B><P>These results provide the first evidence that lymphopenia-associated homeostatic proliferation of autoreactive CD4+ T cells potentiates autoimmune arthritis, and that inhibition of this process protects mice from the development of this pathologic condition.</P>

SPSS 프로그램을 이용한 아산시 하천의 데이터 분석 및 평가에 대한 연구

박상근,김민지,공지희,김소연,윤서은,조대철 순천향대학교 산업기술연구소 2022 순천향 산업기술연구소논문집 Vol.28 No.2

This paper is about a big data analysis for water quality control in two major streams in Asan city. All the data used in this work were collected from publicly open sources such as municipal wastewater treatment facilities and nationwide water data under Department of Environmental Ministry. In the correlation analysis, water quality factors excluding phosphorus are highly correlated with water temperature. On the other hand, in the regression analysis, the water quality factors of Sap-Gyo Stream were more sensitive to water temperature than those of Gok-Gyo Stream.