CD160 serves as a negative regulator of NKT cells in acute hepatic injury

A research team led by Dr. Kyung-Mi Lee, a professor of Biochemistry and Molecular biology, Korean University College of Medicine, presents a new target for acute hepatitis, which may shed light into the development of a new therapy for liver diseases.

Hepatitis is the main cause of liver diseases. In particular, acute hepatitis causes hepatic cells to die with its strong inflammation, which can further lead to acute liver failure. In acute hepatitis, overly activated immune cells can cause liver injury. Therefore, it is essential to identify the immune cells that are activated during the process along with their mechanism of actions.   

CD160 is the receptor expressed on immune cells such as NK cells, NKT cells, and some T cells. It is known to compete BTLA (CD272) in order to bind to the HVEM (CD270) ligand. BTLA, which is expressed on NKT cells had been reported to control excessive immune response by binding to HVEM. So the CD160, which binds to the same ligand of HVEM, was expected to activate NKT cells. Indeed, our team has demonstrated that CD160 functioned as a receptor to activate NK cells (JEM, 2015). However, the currentstudy shows that CD160 is not an NKT cell stimulator but an inhibitor contrary to the expectation. In other words, in acute liver inflammation, there is a rapid increase in the CD160 receptors expressed on NKT cells, which functions like a brake on inflammation. 

In the CD160 deficient mice that we produced in order to study the role of CD160 receptor on NKT cells, α-galactosylceramide (α-GalCer) which is NKT cell-specific ligand was applied to see the liver injury speed up and the AST/ALT level increase in the blood. It is also confirmed that the IL-4 and IFN-g cytokine secreted from the NKT ells increased significantly in both cell and animal levels. It is also proven with the Mixed Bone-Marrow Chimera (CD160KO/WT) that the defect is intrinsic to NKT cells. In addition, when acute hepatitis was induced with Concanavalin A (Con A), there was excessive inflammatory response in the CD160 deficient mice, which led to a significant increase in death rate. Findings of our study indicate that the CD160 receptor is a major factor that suppresses overactive immune reaction initiated by NKT cells. This finding is meaningful in that it can contribute to the development of a new therapy of liver disease especially acute hepatitis, targeting the CD160 receptor.

The research results were published in Journal of Nature Communications under the title, CD160 serves as a negative regulator of NKT cells in acute hepatic injury.

pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/31332204

Nat Commun. 2019 Jul 22;10(1):3258. doi: 10.1038/s41467-019-10320-y.

Blood, "a key to genome," revealed Hantaan virus infection sites

Researchers led by Prof. Jin-Won Song succeeded in building a surveilance system to identify the emergence of Hantaan viruses.

Prof. Jin-Won Song's research team in the Department of Microbiology at Korea University College of Medicine succeeded in conducting active targeted surveillance to track Hantaan virus infection sites for hemorrhagic fever with renal syndrome (HFRS) patients.

Hantaviruses were first discovered in the striped field mouse (Apodemus agrarius) and isolated by Dr. Ho Wang Lee in 1976, well known to cause HFRS. Hantaviruses are transmitted to humans via infected mice and cause renal failure, hemorrhage, thrombocytopenia and shock, posing fatal threats to life. Hantaviruses are evenly spotted around the world as well as in Korea and the domestic species include Hantaan orthohantavirus (HTNV), Seoul orthohantavirus (SEOV), Imjin thottimvirus (MJNV) and Jeju orthohantavirus(JJUV). 

The recent outbreaks of zoonotic Ebola and MERS viruses enhanced caution and needs for active surveillance system to trace new-emerging infectious agents and to identify infection sites. Prof. Jin-Won Song's research team has long been studying genetic features and pathogenicity of hantaviruses and recently succeeded in decrypting the complete genome sequence of HTNV from HFRS patients using Next-generation sequencing (NGS). The study identified the suspected sites of patient infections through epidemiological surveys with patients and phylogeographic analyses based on the geographic locations of HTNV-positive rodents. The results showed that the complete genome of HTNV, epideomiological surveys and targeted trappings enabled effective tracking and surveillance of the emergence of hantaviruses.

The study was published in the online issue of "Clinical Infectious Diseases’ in March with the title "Active Targeted Surveillance to Identify Sites of Emergence of Hantavirus." The journal "Clinical Infectious Diseases" is published by Oxford University Press and the impact factor is 9.117, within the top 3% of journals specialized in infectious diseases in the Journal Citation Reports (JCR). 

The study is also a prime example of global joint research led by researchers from Korea University College of Medicine and the US. 

Prof. Jin-Won Song said "This study will be of much help in preventing and treating viral infections as human health is threatened by zoonotic viruses around the globe. The study showed that subsequent studies and preventive measures are required to deal with zoonotic viral infections in the future. It will greatly contribute to building a prevention and surveillance system of HFRS by tracking and monitoring HTNV infection sites. I also expect that the study will lay the groundwork for targeted surveillance of other zoonotic viral infections."

Prof. Song discovered various types of new viruses including "Imjin thottimvirus" and "Jeju orthohantavirus" since he joined the Department of Microbiology in 1996. He was awarded the National Academy of Sciences of Korea Award in 2011 and the Ho Wang Lee Award in 2013 for his academic achievement. He is a renowned scholar in the field of virus research and is serving as the next President of the International Society of Hantaviruses and the Korean Society of Virology. The Department of Microbiology at Korea University College of Medicine where Prof. Jin-Won Song is affiliated has contributed to the advancement of medical sciences since 1976 when Prof. Ho Wang Lee found hantaviruses for the first time in the world, known as the cause of HFRS, and members of the Department are conducting vigorous research on diverse pathogenic viruses.

pubmed link: https://www.ncbi.nlm.nih.gov/pubmed/30891596

Clin Infect Dis. 2019 Mar 20. pii: ciz234. doi: 10.1093/cid/ciz234.

as the most renowned scholar in medical education and the founder of the OSCE. 

Korea University College of Medicine invited Prof. Ronald M. Harden at the University of Dundee, UK, the most renowned scholar in medical education, to give a lecture at the Yukwangsa Hall on April 10th.

Prof. Harden is the designer of the OSCE (Objective Structured Clinical Examination) adopted to test clinical competence of medical students or interns & residents around the world. He has played a critical role in advancing medical education through scientific studies for more than five decades. He is now serving as General Secretary of the Association for Medical Education in Europe (AMEE) and editor of Medical Teacher, a top journal in medical education.

The topic of Prof. Harden's lecture was "The medical school of the future: Imagine if the impossible isn’t" and he talked about the paradigm change in medical education to nurture doctors who can understand a future society and also about the goals for us to achieve.

First, he called for a transformative change of the paradigm in curriculum planning. He highlighted key concepts and elements of the "Authentic curriculum" such as outcome/competence-based education, just-in-time learning, assessment of competences required in practicing medicine and field-based learning.

Second, he emphasized the "adaptive learning" customizable to individual students, breaking from the traditional "one size fits all" approach. He said that a medical college is not a factory producing standard goods out of the same input materials.

Third, he stressed "collaboration" as a major competence to build in medical education. He emphasized the need to introduce interprofessional education into medical education to become a leader in medical research guiding biomedical industry and provide good care for patients, as the interorganizational and international collaborations among diverse professions are getting more important.

Fourth, he claimed that students are not just a trainee or a consumer but need to play a role as a partner in planning and managing medical curriculum for the advancement of medical education. He called for teachers to diversify their roles into a "curriculum developer" who designs a curriculum for students, a "facilitator" who facilitates learning of students, a "manager" who effectively manages a curriculum, an impartial evaluator and a professor who practices medicine and play a role model for students, not just as a clinical doctor and scholar.

Min-seo Choi, a 1^st year student in the premedical course, said "I asked Prof. Harden a question about the impact of the 4th Industrial Revolution and advances in AI technologies on doctors and about attitudes of students on what to learn. He said that the most important thing is to draw a big picture combining technological advances and occupational changes and prepare to accept technological transformations, which we should actively adopt and employ rather than exploit or be exploited by. I was impressed by the WFME and Prof. Harden’s special lecture where many participants from around the world came to exchange their ideas on medical education, and I felt proud that the event was hosted by Korea University."

Jeong-hyun Lee, a 1st year student in the premedical course, said "I have been to the WFME last Sunday. It was an excellent opportunity to learn the current status of medical education. I have been very interested in the advancement mechanism of medical education around the globe and the special lecture by Prof. Harden was helpful to partially answering my questions on the topic. I expect these experiences will help my study in medicine by providing a broader perspective on the world."