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4-1BB functions as a survival factor in dendritic cells.
Choi, Beom K,Kim, Young H,Kwon, Patrick M,Lee, Sang C,Kang, Sang W,Kim, Moon S,Lee, Myoung J,Kwon, Byoung S Williams Wilkins 2009 JOURNAL OF IMMUNOLOGY Vol.182 No.7
<P>4-1BB (CD137) is expressed on dendritic cells (DCs) and its biological function has remained largely unresolved. By comparing 4-1BB-intact (4-1BB(+/+)) and 4-1BB-deficient (4-1BB(-/-)) DCs, we found that 4-1BB was strongly induced on DCs during the maturation and that DC maturation was normal in the absence of 4-1BB. However, DC survival rate was low in the absence of 4-1BB, which was due to the decreased Bcl-2 and Bcl-x(L) in 4-1BB(-/-) DCs compared with 4-1BB(+/+) DCs after DC maturation. Consistent with these results, 4-1BB(-/-) DCs showed an increased turnover rate in steady state and more severely decreased in spleen by injecting LPS compared with 4-1BB(+/+) DCs. When OVA-pulsed DCs were adoptively transferred to recipient mice along with OVA-specific CD4(+) T cells, 4-1BB(-/-) DCs did not properly migrate to the T cell zone in lymph nodes and poorly induced proliferation of CD4(+) T cells, although both DCs comparably expressed functional CCR7. Eventually, 4-1BB(-/-) DCs generated a reduced number of OVA-specific memory CD4(+) T cells compared with 4-1BB(+/+) DCs. To further assess the role of 4-1BB on DC longevity in vivo, 4-1BB(+/+) and 4-1BB(-/-) C57BL/6 were administrated with Propionibacterium acnes that develop liver granuloma by recruiting DCs. Number and size of granuloma were reduced in the absence of 4-1BB, but the inflammatory cytokine level was comparable between the mice, which implied that the granuloma might be reduced due to the decreased longevity of DCs. These results demonstrate that 4-1BB on DCs controls the duration, DC-T interaction, and, therefore, immunogenicity.</P>
Choi, Beom K.,Hwang, Sun H.,Kim, Yu I.,Singh, Rohit,Kwon, Byoung S. Elsevier 2019 Cytokine Vol.113 No.-
<P><B>Abstract</B></P> <P>The Hyaluronic Acid-rich Node and Duct System (HAR-NDS or NDS), Primo Vascular System (PVS) or Bonghan System (BHS), is thought to be a third circulatory system independent of the blood and lymphatic systems and a structure of connected nodes and ducts. Although it seems to be part of the immune system as it is enriched with cells of innate immunity, little is known about its immunological roles. We performed cellular profiling and secretome analysis of NDS in a steady state and under TLR2- or TLR4-mediated local inflammation, and found that the NDS is pre-dominantly enriched with the myeloid cells, selectively attracts the inflammatory macrophages and neutrophils, has a flexible structure just like the lymph node, and is structured with the fibroblastic reticular cells and reticular network. NDS dominantly harbored the myeloid cells in both steady and activated status, and secreted various types of inflammatory cytokines by proinflammatory stimuli. These results suggest that NDS is the lymphoid structure for the innate immunity and plays an intermediary role in the innate immune cell-mediated local inflammation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> HAR-NDS pre-dominantly enriched with the myeloid cells rather than lymphocytes. </LI> <LI> Inflammatory stimuli produce inflammatory cytokines and chemokines from HAR-NDS. </LI> <LI> Inflammatory stimuli induce the rapid and transient swelling of HAR-NDS. </LI> <LI> HAR-NDS has a flexible structure just like the lymph node. </LI> </UL> </P>
4-1BB signaling activates glucose and fatty acid metabolism to enhance CD8+ T cell proliferation
Choi, Beom K,Lee, Do Y,Lee, Don G,Kim, Young H,Kim, Seon-Hee,Oh, Ho S,Han, Chungyong,Kwon, Byoung S Springer Science and Business Media LLC 2017 CELLULAR AND MOLECULAR IMMUNOLOGY Vol.14 No.9
<P>4-1BB (CD137) is a strong enhancer of the proliferation of CD8(+) T cells. Since these cells require increased production of energy and biomass to support their proliferation, we hypothesized that 4-1BB signaling activated glucose and fatty acid metabolism. We found that treatment with agonistic anti-4-1BB mAb promoted the proliferation of CD8(+) T cells in vitro, increasing their size and granularity. Studies with a glycolysis inhibitor and a fatty acid oxidation inhibitor revealed that CD8(+) T cell proliferation required both glucose and fatty acid metabolism. Anti-4-1BB treatment increased glucose transporter 1 expression and activated the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK)-acetyl-CoA carboxylase (ACC) signaling pathway, which may be responsible for activating the metabolism of glucose and fatty acids. We also examined whether blocking glucose or fatty acid metabolism affected cell cycle progression and the anti-apoptotic effect of 4-1BB signaling. The increase of anti-apoptotic factors and cyclins in response to anti-4-1BB treatment was completely prevented by treating CD8(+) T cells with the fatty acid oxidation inhibitor, etomoxir, but not with the glycolysis inhibitor, 2-deoxy-Dglucose. We conclude that anti-4-1BB treatment activates glucose and fatty acid metabolism thus supporting the increased demand for energy and biomass, and that fatty acid metabolism plays a crucial role in enhancing the cell cycle progression of anti-CD3-activated CD8(+) T cells in vitro and the anti-apoptotic effects of 4-1BB signaling on these cells.</P>
Choi, Beom K.,Kim, Young H.,Lee, Don G.,Oh, Ho S.,Kim, Kwang H.,Park, Sang H.,Lee, Jinsun,Vinay, Dass S.,Kwon, Byoung S. The American Association of Immunologists, Inc. 2015 JOURNAL OF IMMUNOLOGY Vol.194 No.4
<P>4-1BB signals are considered positive regulators of T cell responses against viruses and tumors, but recent studies suggest that they have more complex roles in modulating T cell responses. Although dual roles of 4-1BB signaling in T cell responses have been suggested, the underlying mechanisms are still not fully understood. In this study, we tested whether 4-1BB expression affected T cell responses differently when expressed in myeloid versus lymphoid cells in vivo. By assessing the proliferation of 4-1BB<SUP>+/+</SUP> and 4-1BB<SUP>−/−</SUP> T cells in lymphocyte-deficient RAG2<SUP>−/−</SUP> and RAG2<SUP>−/−</SUP>4-1BB<SUP>−/−</SUP> mice, we were able to compare the effects on T cell responses of 4-1BB expression on myeloid versus T cells. Surprisingly, adoptively transferred T cells were more responsive in tumor-bearing RAG2<SUP>−/−</SUP>4-1BB<SUP>−/−</SUP> mice than in RAG2<SUP>−/−</SUP> mice, and this enhanced T cell proliferation was further enhanced if the T cells were 4-1BB deficient. Dendritic cells (DCs) rather than NK or tissue cells were the myeloid lineage cells primarily responsible for the enhanced T cell proliferation. However, individual 4-1BB<SUP>−/−</SUP> DCs were less effective in T cell priming in vivo than 4-1BB<SUP>+/+</SUP> DCs; instead, more DCs in the secondary lymphoid organs of RAG2<SUP>−/−</SUP>4-1BB<SUP>−/−</SUP> mice appeared to induce the enhanced T cell proliferation by producing and transpresenting more IL-15. Therefore, we conclude that in vivo 4-1BB signaling of myeloid cells negatively regulates peripheral T cell responses by limiting the differentiation of DCs and their accumulation in secondary lymphoid organs.</P>
Kim, Beom Jin,Lee, Jungkyu K.,Choi, Insung S. The Royal Society of Chemistry 2019 Chemical communications Vol.55 No.15
<P>Inspiration from the iron gall ink leads to the efficient formation of Fe(iii)-tannic acid coacervate particles inside the phase-separated microdroplets that are derived from the aqueous PEG/dextran liquid-liquid phase separation system. This hierarchical self-assembly, in aid of the protein affinity of tannic acid, makes it possible to compartmentalize and condense proteins into a localized, compact space in the microdroplets.</P>
아토피피부염 환자에서 국소 피메크로리무스의 효과와 순응도에 관한 다기관 설문조사
김범준 ( Beom Joon Kim ),김명남 ( Myeung Nam Kim ),김규한 ( Kyu Han Kim ),김도원 ( Do Won Kim ),노영석 ( Young Suck Ro ),박천욱 ( Chun Wook Park ),이승철 ( Seung Chul Lee ),이애영 ( Ai Young Lee ),최지호 ( Jee Ho Choi ),이광훈 ( K 대한피부과학회 2008 대한피부과학회지 Vol.46 No.10
Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease that`s influenced by many genetic and environmental factors. Various treatment modalities are being applied for AD, including phototherapy, topical applicants and systemic agents. However, there has been no mass survey in Korea concerning the compliance of patients` to use their prescribed medication, which might influence the clinical efficacy of the physicians` treatment. Objective: The purpose of the present study is to evaluate the efficacy, safety and patient compliance with using topical pimecrolimus to treat AD. Methods: We reviewed the medical recordings, laboratory profiles, clinical severity scoring and photographs of AD patients at 9 general hospitals in Seoul and the local area of Korea. Interviews with the patients and a telephone survey were also done. Those patients who weren`t perscribed topical applicants or those who did not use topical pimecrolimus or steroid within 6 months were excluded from this study. Results: Topical pimecrolimus cream effectively controlled AD with a reduction of the EASI score from baseline 13.75 to 11.39 at 2 weeks and 4.46 at 10 weeks of topical pimecrolimus application. When topical pimecrolimus cream was applied for more than 12 months it significantly suppressed the recurrence and reactivation of AD (p<0.05). Although 22.6% of the patients complained of adverse effects, these were all transient and they did not evoke significant medical problems. Using topical pimecrolimus cream did not show significant adverse effects or complications. Conclusion: Topical pimecrolimus might well be an effective treatment modality for treating AD when patients show good compliance for applying the cream. (Korean J Dermatol 2008;46(10):1357∼1361)
2모작 적응 준조숙 내탈립 대립 다수성 콩 품종 ‘선유2호’
강범규(Beom Kyu Kang),서정현(Jeong Hyun Seo),김현태(Hyun Tae Kim),백인열(In Youl Baek),최만수(Man Soo Choi),박장환(Chang Hwan Park),윤홍태(Hong Tae Yun),신상욱(Sang Ouk Shin),김홍식(Hong Sik Kim),곽도연(Do Yeon Gwak),고지연(Ji Yeon K 한국육종학회 2022 한국육종학회지 Vol.54 No.4
A soybean cultivar, “Seonyu2ho” for double cropping using soy-paste and tofu was developed in 2011 using the pedigree method by crossing “Milyang235ho” and “Jungmo3004ho.” A promising line, YS2441-B-2S-11-3, was selected and named as “Milyang334.” It demonstrated prominent early maturing, shattering resistance, and high yield in regional yield trials (RYTs) from 2017 to 2019, and was released by the name “Seonyu2ho.” The cultivar showed a determinate growth habit, white flowers, grey pubescence, yellow seed coat, yellow hilum, flat-spherical seed shape, and large seed size (27.9 g per 100 seeds). “Seonyu2ho” matured on October 5 (112-growing day cycle) in RYT and was suitable for double cropping with winter crops, such as wheat, barley, and onion. It was resistant to bacterial pustule and s oyb ean mosaic virus and tolerant to lodging in fields. Particularly, “Seonyu2ho” showed a high yield (3.34 ton/ha) and shattering resistance, even if the previously developed early matured cultivars exhibited low yield and easy shattering. Overall, “Seonyu2ho” can contribute to stable soybean production in double cropping.