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[2019/07/02] The Chen Team Discovered an “Innate Immune Checkpoint”

NYMU's Institute of Clinical Medicine held a press conference introducing this important research result


The discovery of an “acquired immune checkpoint” has inspired research into cancer immunotherapy and the result was the awarding of the Nobel Prize to the researchers involved. NYMU's Institute of Clinical Medicine team led by Professor Chen has just discovered that, in addition to the acquired immune checkpoint present in human immune cells maintained above, there is also an “innate immune checkpoint” that is initiated in white blood cells even earlier. This discovery complements the results that led to winning of the Nobel Prize in Physiology or Medicine, and NYMU results have just been published in the journal “Cell Host & Microbe” on April 10th, 2019.


Professor Chen described how the immune system in the human body can be divided into “innate immunity” and “acquired immunity”. Such an understanding is currently used in cancer immunotherapy involving the PD-2 and CTLA-4 inhibitors. This form of inhibitor serves as a “break system” targeting acquired immunity T cells and can also help activate the immune system in order to achieve the elimination of a tumor. This discovery by a Japanese scientist resulted in the 2018 Noble Medicine Prize being awarded for this research. However, quite different to the way acquired immunity works, innate immunity is the first line of defense against foreign bacterial infection. Professor Chen and his team discovered using white blood cells of humans and mice that immune check points are not only located in T lymphocyte cells, but also in mononuclear cells, macrophages, dendritic cells, etc. These cells serve as the first line of defense and provide innate immunity via our white blood cells. These findings filled a significant hole in the research that led to the awarding of the 2019 Noble Medicine Prize.


Professor Chen’s team unveils the concept of the NLRP12 checkpoint


Professor Chen remarked “Immune check points act as a break system, preventing our immune system from over-activating, which, if it happens, can result in the immune system attacking our own cells causing autoimmune disease. Immune therapy uses drugs to force closed the break system, which allows T lymphocyte cells to become active and attack cancer cells, which results in better cancer treatment. Through a series of experiments that deletes the NLRP12 gene in innate immune white blood cells and in a nude mouse experimental platform, her team found that changes to the expression level of the innate immune checkpoint gene NLRP12 had the ability to activate or inhibit the production of type 1 interferon by macrophages and dendritic cells. Such ability confirms the presence of immune checkpoints in innate immunity white blood cells, rather than in only T lymphocytes. Furthermore, intestinal bacteria do not affect the biological functioning of these innate immunity checkpoints.


In addition to the mouse model, the team also confirmed that the NLRP12 innate immune checkpoint is also widely expressed in a variety of innate immune cells in humans and does have the ability to regulate the production of antiviral type 1 interferons in our species. In the past, scientists only knew that the NLRP12 protein is beneficial to the growth of specific strains of intestinal bacteria and the regulation the intestinal flora, and that this gene is associated with reduced intestinal inflammation and colorectal cancer. Professor Chen and her team's discovery have not only unveiled a major function of NLRP12 function, but they have also discovered the concept of innate immune checkpoints.


Professor Chen remarked that the immunity balance in mammals plays a pivotal role in maintaining a constant body state. After a pathogen infects our body, white blood cell secrete type 1 interferons, which prevents further infection and the development of an inflammatory response. If NLRP12 innate immune checkpoint does not stop the development of our innate immunity in time, our immune defense system will begin to attack our normal cells, which can lead to a cytokine storms, and the possibility of organ failure and death. The discovery of these innate immunity checkpoints opened up a window of opportunity for the study of pathogenesis of autoimmune diseases. In the future, such diseases may begin to be treated using immunotherapy in a similar manner to cancer.


nstitute of Clinical Medicine Associate Professor Chen (right) and her research team


In addition to National Yang-Ming University, other participants in this research project were Taipei Veterans General Hospital's Department of Pathology, Rheumatology, and The University of North Carolina at Chapel Hill, USA. This project received funding from the Ministry of Science and Technology, Ministry of Education Office of Higher Education Sprout Project and National Yang Ming University Faculty of Medicine “Medical Development Project”.


For the full paper and related video, please view the link below: