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STING regulates BCR signaling in normal and malignant B cells

Cellular & Molecular Immunology 2021年第4期18卷 1016-1031页

作者： Chih-Hang Anthony Tang Avery C.Lee Shiun Chang Qin Xu Andong Shao Yun Lo Walker T.Spalek Javier A.Pinilla-lbarz Juan R.Del Valle Chih-Chi Andrew Hu the wistar institute 3601 Spruce StreetPhiladelphiaPA 19104USA Department of Malignant Hematology H.Lee Moffitt Cancer Center&Research InstituteTampaFL 33612USA Department of Chemistry&Biochemistry University of Notre DameNotre DameIN 46556USA

STING is an endoplasmic reticulum(ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type Ⅰ interferons;however,the role of STING in B cell receptor(BCR)signaling remains *** generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded membrane-bound IgM,Ig a and Igβ via SEL1L/HRD1-mediated ER-associated degradation(ERAD).B cells with activated STING were thus less capable of responding to BCR activation by phosphorylating Igα and Syk than those without activated *** immunized with T-independent antigens,STING V154M mice produced significantly fewer antigen-specific plasma cells and antibodies than immunized wild-type(WT)*** further generated B cell-specific STING^(KO) mice and showed that STING^(KO) B cells indeed responded to activation by transducing stronger BCR signals than their STING-proficient *** B cell-specific STING^(KO) mice were T-independently immunized,they produced significantly more antigen-specific plasma cells and antibodies than immunized STIN^(WT)*** both human and m ouse IGHV-unmutated malignant chronic lymphocytic leukemia(CLL)cells downregulated the expression of STING,we explored whether STING downregulation could contribute to the well-established robust BCR signaling phenotype in malignant CLL *** generated a STING-deficient CLL mouse model and showed that STING-deficient CLL cells were indeed more responsive to BCR activation than their STING-proficient *** results revealed a novel B cell-intrinsic role of STING in negatively regulating BCR signaling in both normal and malignant B cells.

关键词： STING BCR ER-associated degradation CLL Plasma cells

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用抗雌激素药物改善皮肌炎皮疹

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世界核心医学期刊文摘（皮肤病学分册） 2006年第3期2卷 31-32页

作者： Sereda D. Werth V.P. 刘艳 2 Rhoads pavilion Department of Dermatology 36th and Spruce Streets Philadelphia PA19104United States Dr

Background: Dermatomyositis (DM) is an autoimmune disorder that occurs more often inwomen than men and causes highly symptomatic and inflammatory cutaneous and proximal muscle disease. Corticosteroids have been the treatment of choice for myositis in DM, and antimalarial agents for the skin disease of DM, with methotrexate sodium, azathioprine, mycophenolate mofetil, cyclosporine, and intravenous immunoglobulin used as steroid-sparing agents. Recently, reports supporting a role for anti-tumor necrosis factorα (TNF-α ) therapy in the treatment of DM have emerged. Observations: We describe 2 women who experienced an improvement in their DM-associated skin eruptions while taking antiestrogen medication. the first patient was taking tamoxifen, a selective estrogen receptor modulator that has been found to have anti-TNF-α properties. the second was taking anastrozole, an aromatase inhibitor. When tamoxifen therapy was discontinued after 4 years of use in the first patient, her DM rash worsened and remained difficult to control with conventional immunosuppressant medication. Conclusions: With the limited number of therapies available to manage DM skin eruptions, the discovery of novel agents effective in treating this disease is vital. Using antiestrogen medication in women with DM may result in a significant improvement in their rash, possibly via the inhibition of TNF-α production by immune or other cells. Further investigation into the use of antiestrogen therapy in DM is merited to evaluate longterm risks and benefits.

关键词：抗雌激素药物皮肌炎肿瘤坏死因子-α(TNF-α) 选择性雌激素受体调节剂静脉注射免疫球蛋白自身免疫性疾病皮疹女性患者抗TNF-α 皮肤损害

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A New Specimen of Liaoceratops yanzigouensis(Dinosauria:Neoceratopsia)from the Early Cretaceous of Liaoning Province,China

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Acta Geologica Sinica(English Edition) 2007年第6期81卷 898-904页

作者： YOU Hailu Kyo TANOUE Peter DODSON institute of Geology Chinese Academy of Geological Sciences 26 Baiwanzhuang Road Beijing 100037 China Department of Earth and Environmental Science University of Pennsylvania 240 S. 33rd Street Philadelphia PA 19104-6316 USA School of Veterinary Medicine University of Pennsylvania 3800 Spruce Street Philadelphia PA 19104-6045 USA

A new specimen of basal neoceratopsian dinosaur Liaoceratops yanzigouensis is described. the specimen comes from the Lujiatun Bed of the Lower Cretaceous Yixian Formation in Beipiao City of western Liaoning Province, and is represented by a very well preserved three-dimensional partial skull and mandible. It is also the smallest among the three specimens of L. yanzigouensis, and several features in the new specimen, such as the short preorbital length and the round rostroventral orbital rim, can be ontogenetically-related. the superb exposure of the palatal complex may be caused by the removing of its brain by a small predator in the contemporary Jehol Biota.

关键词： Dinosauria Neoceratopsia Early Cretaceous Yixian Formation Liaoning Province China

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单克隆抗体用于固定组织结合一种重糖基蛋白的免疫过氧化物酶染色

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细胞与分子免疫学杂志 1986年第Z1期 148-148页

作者： Ross A.H. ALK Tnson BA. Ernst C.E. Christ B.F.D. Steplewski Z Koproaski H. 郑涛 the wistar institute 36th and spruce streets philadelphia pa 19104 the wistar institute 36th and spruce streets philadelphia pa 19104 the wistar institute 36th and spruce streets philadelphia pa 19104 the wistar institute 36th and spruce streets philadelphia pa 19104 the wistar institute 36th and spruce streets philadelphia pa 19104 the wistar institute 36th and spruce streets philadelphia pa 19104

一种新的抗黑色素瘤的单克隆抗体业已制成,它们专用于固定组织的免疫过氧化物酶染色,早期杂交瘤培养基上清液可用来测定石蜡包埋组织块中的黑色素瘤细胞的反应性。这三种抗体(ME491,ME492、ME493)具有相似的性质,即可与浅层扩散的黑色... 详细信息

一种新的抗黑色素瘤的单克隆抗体业已制成,它们专用于固定组织的免疫过氧化物酶染色,早期杂交瘤培养基上清液可用来测定石蜡包埋组织块中的黑色素瘤细胞的反应性。这三种抗体(ME491,ME492、ME493)具有相似的性质,即可与浅层扩散的黑色素瘤细胞具有强烈的反应性（31/33）,而对分化不良瘤（10/11）及转移的黑色瘤（5/10）则较弱。巨噬细

关键词：免疫过氧化物酶染色单克隆抗体

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On a New Genus of Basal Neoceratopsian Dinosaur from the Early Cretaceous of Gansu Province, China

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Acta Geologica Sinica(English Edition) 2005年第5期79卷 593-597页

作者： YOU Hailu LI Daqing JI Qiang Matthew C. LAMANNA Peter DODSON institute of Geology Chinese Academy of Geological Sciences Beijing 100037 China Fossil Research and Development Center of the third Geology and Mineral Resources Exploration Academy of Gansu Province Lanzhou Gansu 730050 China Section of Vertebrate paleontology Carnegie Museum of Natural History 4400 Forbes Avenue Pittsburgh PA 15213 USA Department of Animal Biology School of Veterinary Medicine University of Pennsylvania 3800 Spruce Street Philadelphia PA 19104 USA

A new genus and species of basal neoceratopsian dinosaur, Auroraceratops rugosus, is reported based on material from the Early Cretaceous Xinminpu Group in the Gongpoquan Basin of Gansu Province, China. Auroraceratops is represented by a nearly complete skull and low jaws, and different greatly from all other neoceratopsians by its considerable breadth of the nasals, fungi form expansion of the dorsal end of the lacrimal, highly developed rugosity of the jugal, dentary and surangular, and inflated, striated premaxillary teeth. the finding of Auroraceratops adds diversity and helps elucidate the evolution of basal neoceratopsian dinosaurs.

关键词： Dinosauria Neoceratopsia Early Cretaceous Xinminpu Group Gongpoquan Basin Gansu Province

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Sézary综合征患者临床病情变化与CD4^+CD26^-淋巴细胞百分数变化的关系

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世界核心医学期刊文摘（皮肤病学分册） 2005年第12期1卷 10-11页

作者： Introcaso C.E. Hess S.D. Kamoun M. A.H. Rook 刘芯 Dr. Department of Dermatology 2Rhoads Pavilion 3400 Spruce St Philadelphia PA 19104 United States

Background: Because there are currently many effective therapies available for Sé zary syndrome, close monitoring of disease progression is required in order for a clinician to know when to institute or change an intervention. It has been our clinical experience that changes in patients’ CD4+ CD26- T- cell populations of peripheral blood lymphocytes herald changes in their clinical status. Objective: Our purpose was to evaluate whether a change in patients’ CD4+ CD26- population of T cells presages a change in their clinical status. We also sought to investigate the association between a change in Tcell populations that are CD4+ CD7- , CD8+ , CD56+ , and the CD4 + /CD8+ T- cell ratio and a change in the patient’ s clinical status. Methods: We conducted a retrospective chart review analysis of 21 patients with Sé zary syndrome who had flow cytometry, usually including levels of CD4+ CD26- , CD4+ CD7- , CD8+ , CD56+ , and CD4+ /CD8+ ratios measured at two time periods, 12 weeks apart. Results: We report two cases in which changes in patients’ clinical status were preceded by several weeks by a change in their CD4+ CD26- level. We report weak associations between a decreasing CD4+ CD26- T- cell population, a decreasing CD4+ CD7- population, an increasing CD56+ population, and an improving clinical status. We also report stronger associations between both a decreasing CD8+ population and an increasing CD4+ /CD8+ ratio and a worsening clinical status. Limitations: the study was limited by the number of patients and the time period over which the study was conducted. In addition, varying configurations of CD4+ CD26- T- cell populations were observed that may have limited the utility of this measurement. Conclusions: Flow cytometry assays of patients’ blood and, in particular, measurement of the CD4+ CD26- population of lymphocytes over time may be a valuable tool for monitoring patients with Sé zary syndrome. there exist varying configurations of CD26 T lymphocytes that m

关键词：细胞百分数 CD26 CD4 zary 临床病情淋巴细胞数流式细胞技术流式细胞仪图表分析外周血淋巴细胞

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