Faculty Profiles - katsuyama eri

Papers - katsuyama eri

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痛風性関節炎、特発性間質性肺炎発症後に多発脳梗塞を呈した顕微鏡的多発血管炎(MPA)の1例

堀口裕紀, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

横隔膜挙上に伴う呼吸困難を合併した巨細胞性動脈炎(GCA)の一例

松岡雅人, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 755 - 755 2022.3

大型血管炎が疑われた大動脈周囲悪性リンパ腫の1例

道廣麻友, 勝山隆行, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 楢崎真理子, 佐田憲映, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

初発から40年後に診断に至った炎症症候持続TNF受容体関連周期性症候群の一例

高嶋香菜子, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 756 - 756 2022.3

高安動脈炎が疑われたがPET-CTを契機に希少疾患であるシトステロール血症と判明した一例

中土井崇人, 勝山恵理, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 宮脇義亜, 大橋敬司, 勝山隆行, 楢崎真理子, 松本佳則, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 672 - 672 2022.3

COVID-19ワクチン接種後に脊椎関節炎が顕在化した一例

志田原健太, 松本佳則, 松本和也, 廣瀬啓, 中土井崇人, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 627 - 627 2022.3

動眼神経麻痺を発症した巨細胞性動脈炎の一例

清水崇司, 勝山隆行, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 楢崎真理子, 佐田憲映, 松本佳則, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 755 - 755 2022.3

爪形成不全と肘関節脱臼を伴った関節リウマチの1例

増田倫敦, 松本佳則, 松本和也, 廣瀬啓, 志田原健太, 縄稚翔一, 中土井崇人, 浅野洋介, 片山祐, 大橋敬司, 宮脇義亜, 勝山恵理, 勝山隆行, 楢崎真理子, 佐田憲映, 和田淳

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 754 - 754 2022.3

臨床(内科)・症例報告大学病院に勤務する膠原病・リウマチ内科医のバーンアウト(燃え尽き症候群)とグリットとの関連 TRUMP2-SLE研究

宮脇義亜, 佐田憲映, 志田原健太, 縄稚翔一, 浅野洋介, 片山祐, 大橋敬司, 勝山恵理, 勝山隆行, 楢崎真理子, 松本佳則, 小黒奈緒, 矢嶋宣幸, 吉見竜介, 下島恭弘, 和田淳, 栗田宜明

日本リウマチ学会総会・学術集会プログラム・抄録集 66回 435 - 435 2022.3

Potential of a Novel Chemical Compound Targeting Matrix Metalloprotease-13 for Early Osteoarthritis: An In Vitro Study. International journal

Junko Inagaki, Airi Nakano, Omer Faruk Hatipoglu, Yuka Ooka, Yurina Tani, Akane Miki, Kentaro Ikemura, Gabriel Opoku, Ryosuke Ando, Shintaro Kodama, Takashi Ohtsuki, Hirosuke Yamaji, Shusei Yamamoto, Eri Katsuyama, Shogo Watanabe, Satoshi Hirohata

International journal of molecular sciences 23 ( 5 ) 2022.2

Language：English Publishing type：Research paper (scientific journal)

Osteoarthritis is a progressive disease characterized by cartilage destruction in the joints. Matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) play key roles in osteoarthritis progression. In this study, we screened a chemical compound library to identify new drug candidates that target MMP and ADAMTS using a cytokine-stimulated OUMS-27 chondrosarcoma cells. By screening PCR-based mRNA expression, we selected 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide as a potential candidate. We found that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated IL-1β-induced MMP13 mRNA expression in a dose-dependent manner, without causing serious cytotoxicity. Signaling pathway analysis revealed that 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide attenuated ERK- and p-38-phosphorylation as well as JNK phosphorylation. We then examined the additive effect of 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide in combination with low-dose betamethasone on IL-1β-stimulated cells. Combined treatment with 2-(8-methoxy-2-methyl-4-oxoquinolin-1(4H)-yl)-N-(3-methoxyphenyl) acetamide and betamethasone significantly attenuated MMP13 and ADAMTS9 mRNA expression. In conclusion, we identified a potential compound of interest that may help attenuate matrix-degrading enzymes in the early osteoarthritis-affected joints.

DOI： 10.3390/ijms23052681

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Skeletal muscle heme oxygenase-1 activity regulates aerobic capacity. International journal

Rodrigo W Alves de Souza, David Gallo, Ghee Rye Lee, Eri Katsuyama, Alexa Schaufler, Janick Weber, Eva Csizmadia, George C Tsokos, Lauren G Koch, Steven L Britton, Ulrik Wisløff, Patricia C Brum, Leo E Otterbein

Cell reports 35 ( 3 ) 109018 - 109018 2021.4

Language：English Publishing type：Research paper (scientific journal)

Physical exercise has profound effects on quality of life and susceptibility to chronic disease; however, the regulation of skeletal muscle function at the molecular level after exercise remains unclear. We tested the hypothesis that the benefits of exercise on muscle function are linked partly to microtraumatic events that result in accumulation of circulating heme. Effective metabolism of heme is controlled by Heme Oxygenase-1 (HO-1, Hmox1), and we find that mouse skeletal muscle-specific HO-1 deletion (Tam-Cre-HSA-Hmox1fl/fl) shifts the proportion of muscle fibers from type IIA to type IIB concomitant with a disruption in mitochondrial content and function. In addition to a significant impairment in running performance and response to exercise training, Tam-Cre-HSA-Hmox1fl/fl mice show remarkable muscle atrophy compared to Hmox1fl/fl controls. Collectively, these data define a role for heme and HO-1 as central regulators in the physiologic response of skeletal muscle to exercise.

DOI： 10.1016/j.celrep.2021.109018

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Association of explanatory histological findings and urinary protein and serum creatinine levels at renal biopsy in lupus nephritis: a cross-sectional study. International journal

Eri Katsuyama, Yoshia Miyawaki, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu-Asano, Michiko Morishita, Keiji Ohashi, Haruki Watanabe, Takayuki Katsuyama, Mariko Narazaki, Yoshinori Matsumoto, Jun Wada

BMC nephrology 21 ( 1 ) 208 - 208 2020.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The aim of the present study was to evaluate the association between the histology of active and chronic lesions and urinary protein and serum creatinine (SCr) levels, as common clinical endpoints in clinical trials for lupus nephritis (LN). METHODS: In total, 119 patients diagnosed with LN class III, IV, and V, as defined by the International Society of Nephrology/Renal Pathology Society, between 1990 and 2015, were enrolled in the present study. Multiple regression analysis was performed to explore semi-quantitative histological variables associated with urinary protein and SCr levels. RESULTS: The mean age of the enrolled patients was 45 years, and 79% were female. The mean SCr and mean urinary protein levels at the time of renal biopsy were 0.87 mg/dl and 3.00 g/gCr, respectively. Class IV (71%) was the most common type of LN followed by class III (17%), and class V (13%). Multicollinearity was confirmed between monocellular infiltration (variance inflation factor [VIF] = 10.22) and interstitial fibrosis (VIF = 10.29), and between karyorrhexis (VIF = 4.14) and fibrinoid necrosis (VIF = 4.29). Fibrinoid necrosis and monocellular infiltration were subsequently excluded, and multiple regression analysis revealed that only the urinary protein level was correlated with wire loop lesions (β-coefficient [β]: 1.09 and confidence interval [CI]: 0.35 to 1.83), and that the SCr level was correlated with glomerular sclerosis (β: 1.08 and CI: 0.43 to 1.74). CONCLUSION: As urinary protein and SCr levels were not quantitatively associated with active lesions, they may not accurately reflect the response to remission induction therapy in patients with LN.

DOI： 10.1186/s12882-020-01868-9

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Risk Factors for Chronic Damage Accumulation Across Different Onset Eras in Systemic Lupus Erythematosus: A Cross-sectional Analysis of a Lupus Registry of Nationwide Institutions (LUNA).

Keiji Ohashi, Ken-Ei Sada, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu Asano, Yoshia Miyawaki, Michiko Morishita, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori-Watanabe, Tomoko Kawabata, Nobuyuki Yajima, Jun Wada

Acta medica Okayama 74 ( 3 ) 191 - 198 2020.6

Language：English Publishing type：Research paper (scientific journal)

Chronic damage accumulation affects not only mortality but also quality of life in patients with systemic lupus erythematosus (SLE). Risk factors for chronic damage were explored in SLE through different onset eras. Two hundred forty-five patients at Okayama University Hospital and Showa University Hospital were divided into three groups based on the onset era: a past-onset group (onset before 1995; n=83), middle-onset group (1996-2009; n=88), and recent-onset group (after 2010; n=74). The mean Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score as an index of chronic damage was 1.93, 1.24, and 0.53 in the past-, middle-, and recent-onset groups, respectively. In the pastonset group, the total SDI score was significantly associated with glucocorticoid monotherapy by linear regression analysis (β-coefficient [β]=0.63; 95% confidence interval [CI], 0.21-1.05) and C-reactive protein levels (β=0.67; 95% CI, 0.27-1.07). In the middle-onset group, the total SDI score was significantly associated with the SLE Disease Activity Index at registration (β=0.09; 95% CI, 0.03-0.12). Reducing the accumulation of chronic damage in SLE patients might be possible with the concomitant use of immunosuppressants and tight control of disease activity.

DOI： 10.18926/AMO/59949

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The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections. International journal

Eri Katsuyama, Abel Suarez-Fueyo, Sean J Bradley, Masayuki Mizui, Ana V Marin, Lama Mulki, Suzanne Krishfield, Fabio Malavasi, Joon Yoon, Shannan J Ho Sui, Vasileios C Kyttaris, George C Tsokos

Cell reports 30 ( 1 ) 112 - 123 2020.1

Language：English Publishing type：Research paper (scientific journal)

Patients with systemic lupus erythematosus (SLE) suffer frequent infections that account for significant morbidity and mortality. T cell cytotoxic responses are decreased in patients with SLE, yet the responsible molecular events are largely unknown. We find an expanded CD8CD38high T cell subset in a subgroup of patients with increased rates of infections. CD8CD38high T cells from healthy subjects and patients with SLE display decreased cytotoxic capacity, degranulation, and expression of granzymes A and B and perforin. The key cytotoxicity-related transcription factors T-bet, RUNX3, and EOMES are decreased in CD8CD38high T cells. CD38 leads to increased acetylated EZH2 through inhibition of the deacetylase Sirtuin1. Acetylated EZH2 represses RUNX3 expression, whereas inhibition of EZH2 restores CD8 T cell cytotoxic responses. We propose that high levels of CD38 lead to decreased CD8 T cell-mediated cytotoxicity and increased propensity to infections in patients with SLE, a process that can be reversed pharmacologically.

DOI： 10.1016/j.celrep.2019.12.014

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Deletion of Mir223 Exacerbates Lupus Nephritis by Targeting S1pr1 in Faslpr/lpr Mice. International journal

Sumie Hiramatsu-Asano, Katsue Sunahori-Watanabe, Sonia Zeggar, Eri Katsuyama, Tomoyuki Mukai, Yoshitaka Morita, Jun Wada

Frontiers in immunology 11 616141 - 616141 2020

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: The micro RNAs (miRNAs) and their target mRNAs are differentially expressed in various immune-mediated cells. Here, we investigated the role of Mir223 and sphingosine-1-phosphate receptor 1 (S1pr1) in the pathogenesis of systemic lupus erythematosus. METHODS: We analyzed miRNA and mRNA profiling data of CD4+ splenic T cells derived from MRL/MpJ-Faslpr /J mice. We performed 3' untranslated region (UTR) luciferase reporter gene assay using human umbilical vein endothelial cells (HUVECs). We generated the B6-Mir223-/-Faslpr/lpr mice and the lupus phenotypes were analyzed. RESULTS: In CD4+ splenic T cells, we identified upregulation of miR-223-3p and downregulation of the possible target, S1pr1 by RNA sequencing of MRL/MpJ-Faslpr /J mice. The transfection with miR-223-3p mimic significantly suppressed a luciferase activity in HUVEC treated with a Lentivirus vector containing 3' UTR of S1pr1. The mRNA levels of S1pr1 were significantly decreased after miR-223-3p overexpression. In B6-Mir223-/-Faslpr/lpr mice, the proportion of CD3+ T cells, CD3+CD4-CD8- cells, B cells, plasma cells, and S1PR1+CD4+ T cells in the spleen was significantly increased compared with that in B6-Mir223+/+Faslpr/lpr mice by flow cytometry. B6-Mir223-/-Faslpr/lpr mice demonstrated the elevation of glomerular and renal vascular scores associated with enhanced intraglomerular infiltration of S1PR1+CD4+ T cells. CONCLUSION: Unexpectedly, the deletion of Mir223 exacerbated the lupus phenotypes associated with increased population of S1PR1+CD4+ T in spleen and the enhanced infiltration of S1PR1+CD4+ T cells in inflamed kidney tissues, suggesting compensatory role of Mir223 in the pathogenesis of lupus nephritis.

DOI： 10.3389/fimmu.2020.616141

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Cluster Analysis Using Anti-Aminoacyl-tRNA Synthetases and SS-A/Ro52 antibodies in Patients With Polymyositis/Dermatomyositis. International journal

Keiji Ohashi, Ken-Ei Sada, Yu Nakai, Shun Matsushima, Yosuke Asano, Keigo Hayashi, Yuriko Yamamura, Sumie Hiramatsu, Yoshia Miyawaki, Michiko Morishita, Takayuki Katsuyama, Eri Katsuyama, Haruki Watanabe, Noriko Tatebe, Mariko Narazaki, Yoshinori Matsumoto, Katsue Sunahori Watanabe, Tomoko Kawabata, Jun Wada

Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases 25 ( 6 ) 246 - 251 2019.9

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Although several autoantibodies have been identified for polymyositis/dermatomyositis (PM/DM) diagnosis, the clinical impact of these antibodies is yet to be elucidated. METHODS: Patients with PM/DM at Okayama University Hospital from 2012 to 2016 were historically enrolled, and antibody profiles were analyzed using line immunoassay. Hierarchical cluster analysis was performed based on serological analysis of anti-aminoacyl-tRNA synthetase (ARS) antibodies, including anti-Jo-1, PL-7, PL-12, EJ, OJ, and SS-A/Ro-52 antibodies. Clinical symptoms and relapse proportions were compared among these clusters. RESULTS: Sixty-one patients were enrolled in this study: 28 were diagnosed with PM, and 33 were diagnosed with DM. The following 3 clusters were determined: 1 (n = 10), anti-Jo-1 and anti-SS-A/Ro-52 antibodies double positive (10/10, 100%); 2 (n = 24), anti-SS-A/Ro-52 antibody positive (20/24, 83%), anti-Jo-1 antibody negative (24/24, 100%), and anti-ARS antibodies (excluding anti-Jo-1 antibody) positive (15/24, 63%); and 3 (n = 27), anti-Jo-1 and anti-SS-A/Ro52 antibodies double negative (26/27, 96%). The proportion of patients who relapsed was significantly lower in cluster 3 than it was in clusters 1 and 2 (risk ratio, 0.37; 95% confidence interval, 0.17-0.83; p = 0.026 and risk ratio, 0.42; 95% confidence interval, 0.20-0.89; P = 0.019, respectively). There was no difference in the proportion of relapsed patients between clusters 1 and 2. CONCLUSIONS: Our cluster analysis shows that anti-SS-A/Ro52 or any anti-ARS antibodies or both might be relevant to clinical outcomes.

DOI： 10.1097/RHU.0000000000000836

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SLAMF6 as a Regulator of Exhausted CD8+ T Cells in Cancer. International journal

Burcu Yigit, Ninghai Wang, Elisa Ten Hacken, Shih-Shih Chen, Atul K Bhan, Abel Suarez-Fueyo, Eri Katsuyama, George C Tsokos, Nicholas Chiorazzi, Catherine J Wu, Jan A Burger, Roland W Herzog, Pablo Engel, Cox Terhorst

Cancer immunology research 7 ( 9 ) 1485 - 1496 2019.9

Language：English Publishing type：Research paper (scientific journal)

The tumor microenvironment in leukemia and solid tumors induces a shift of activated CD8+ cytotoxic T cells to an exhausted state, characterized by loss of proliferative capacity and impaired immunologic synapse formation. Efficient strategies and targets need to be identified to overcome T-cell exhaustion and further improve overall responses in the clinic. Here, we took advantage of the Eμ-TCL1 chronic lymphocytic leukemia (CLL) and B16 melanoma mouse models to assess the role of the homophilic cell-surface receptor SLAMF6 as an immune-checkpoint regulator. The transfer of SLAMF6+ Eμ-TCL1 cells into SLAMF6-/- recipients, in contrast to wild-type (WT) recipients, significantly induced expansion of a PD-1+ subpopulation among CD3+CD44+CD8+ T cells, which had impaired cytotoxic functions. Conversely, administering anti-SLAMF6 significantly reduced the leukemic burden in Eμ-TCL1 recipient WT mice concomitantly with a loss of PD-1+CD3+CD44+CD8+ T cells with significantly increased effector functions. Anti-SLAMF6 significantly reduced leukemic burden in the peritoneal cavity, a niche where antibody-dependent cellular cytotoxicity (ADCC) is impaired, possibly through activation of CD8+ T cells. Targeting of SLAMF6 affected tumor growth not only in B cell-related leukemia and lymphomas but also in nonhematopoietic tumors such as B16 melanoma, where SLAMF6 is not expressed. In vitro exhausted CD8+ T cells showed increased degranulation when anti-human SLAMF6 was added in culture. Taken together, anti-SLAMF6 both effectively corrected CD8+ T-cell dysfunction and had a direct effect on tumor progression. The outcomes of our studies suggest that targeting SLAMF6 is a potential therapeutic strategy.

DOI： 10.1158/2326-6066.CIR-18-0664

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Pyruvate kinase M2 is requisite for Th1 and Th17 differentiation. International journal

Michihito Kono, Kayaho Maeda, Irina Stocton-Gavanescu, Wenliang Pan, Masataka Umeda, Eri Katsuyama, Catalina Burbano, Seo Yeon K Orite, Milena Vukelic, Maria G Tsokos, Nobuya Yoshida, George C Tsokos

JCI insight 4 ( 12 ) 2019.6

Language：English Publishing type：Research paper (scientific journal)

Th1 and Th17 are important in the pathogenesis of autoimmune diseases and they depend on glycolysis as a source of energy. T cell antigen receptor signaling phosphorylates a serine/threonine kinase, calcium/calmodulin-dependent protein kinase IV (CaMK4), and promotes glycolysis. Based on these findings we hypothesized that CaMK4 promotes glycolysis. Camk4-deficient CD4+ T cells and cells treated with a CaMK4 inhibitor had less glycolysis compared with their counterparts. Pull-down of CaMK4 and mass spectrometry identified pyruvate kinase muscle isozyme (PKM), the final rate-limiting enzyme in glycolysis, as a binding partner. Coimmunoprecipitation and Western blotting showed that CaMK4 interacts directly with PKM2. Camk4-deficient CD4+ T cells displayed decreased pyruvate kinase activity. Silencing or pharmacological inhibition of PKM2 reduced glycolysis and in vitro differentiation to Th1 and Th17 cells, while PKM2 overexpression restored Th17 cell differentiation. Treatment with a PKM2 inhibitor ameliorated experimental autoimmune encephalomyelitis and CD4+ T cells treated with PKM2 inhibitor or Pkm2-shRNA caused limited disease activity in an adoptive cell transfer model of experimental autoimmune encephalomyelitis. Our data demonstrate that CaMK4 binds to PKM2 and promotes its activity, which is requisite for Th1 and Th17 differentiation in vitro and in vivo. PKM2 represents a therapeutic target for T cell-dependent autoimmune diseases.

DOI： 10.1172/jci.insight.127395

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Regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice derived CD4+ T cells. Reviewed International journal

Sumie Hiramatsu, Katsue S Watanabe, Sonia Zeggar, Yosuke Asano, Yoshia Miyawaki, Yuriko Yamamura, Eri Katsuyama, Takayuki Katsuyama, Haruki Watanabe, Mariko Takano-Narazaki, Yoshinori Matsumoto, Tomoko Kawabata, Ken-Ei Sada, Jun Wada

Scientific reports 9 ( 1 ) 3054 - 3054 2019.2

Language：English Publishing type：Research paper (scientific journal)

Global DNA hypomethylation in CD4+ cells in systemic lupus erythematosus (SLE) was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and Ctse mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was 93.3 ± 2.05% methylated in B6 mice, while 80.0 ± 6.2% methylated and mutated to CGGG in MRL mice. Kaiso is known to bind to mCGCG and we hypothesized that it represses expression of Ctse in B6 mice. The binding of Kaiso to mCGCG site in B6 mice was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or Trichostatin A showed the suppression of binding of Kaiso to mCGCG motif by ChIP-PCR and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.

DOI： 10.1038/s41598-019-38809-y

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Signaling Lymphocytic Activation Molecule Family Member 1 Engagement Inhibits T Cell-B Cell Interaction and Diminishes Interleukin-6 Production and Plasmablast Differentiation in Systemic Lupus Erythematosus. International journal

Maria P Karampetsou, Denis Comte, Abel Suárez-Fueyo, Eri Katsuyama, Nobuya Yoshida, Michihito Kono, Vasileios C Kyttaris, George C Tsokos

Arthritis & rheumatology (Hoboken, N.J.) 71 ( 1 ) 99 - 108 2019.1

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVE: Signaling lymphocytic activation molecule family member 1 (SLAMF1) homophilic interactions promote immunoglobulin production and T cell-B cell cross-talk. SLAMF1 is overexpressed on T and B cells in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the role of SLAMF1 monoclonal antibody (mAb) in modulating T cell-B cell interaction and B cell activation. METHODS: Anti-IgM-prestimulated naive or total B cells from either healthy donors or patients with SLE were cocultured with autologous T cells under CD3/CD28 stimulation, in the presence or absence of the SLAMF1 mAb. Naive B cells were stimulated with anti-IgM and CD40L in the presence of the SLAMF1 antibody. Cytokine production by CD4+ T cells and B cells was examined by flow cytometry and/or quantitative polymerase chain reaction. Plasmablast formation and T cell and B cell conjugates were assessed by flow cytometry. IgG and antinuclear antibody production was determined by enzyme-linked immunosorbent assay. RESULTS: SLAMF1 ligation in a human peripheral blood T cell-B cell culture system reduced the following in both healthy controls and patients with SLE: conjugate formation, interleukin-6 (IL-6) production by B cells, IL-21 and IL-17A production by T cells, and Ig and autoantibody production. Whereas the SLAMF1 mAb directly affected the function of isolated peripheral B cells by decreasing IL-6 and Ig production in vitro, it did not affect cytokine production by isolated T cells stimulated in vitro. CONCLUSION: The SLAMF1 antibody inhibits T cell-B cell interaction and suppresses B cell cytokine production and differentiation, thereby acting as a potential therapeutic tool in the treatment of patients with SLE.

DOI： 10.1002/art.40682

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