Researchers have actually identified a new approach the body immune system utilizes to eliminate cells that do not have CD47 particles marking them as “self”, with dendritic cells directly eliminating these CD47-lacking T cells. This discovery uses a fresh perspective for prospective cancer treatments.
Researchers from Kobe University have actually determined a completely new and unforeseen system through which the body immune system gets rid of cells doing not have particles that identify them as part of the self in mice. This discovery, released in the journal Proceedings of the National Academy of Sciences, might have potential ramifications for cancer therapy.
The immune system consists of many types of cells that work together to eliminate off illness. 2 crucial types are dendritic cells and T cells. Dendritic cells lie in tactical positions throughout the body consisting of the gut and skin, as well as in the lymph nodes, sample their environment and present small parts originated from these samples on their surface area.
T cells examine these samples and if they acknowledge them as foreign (or “non-self”), they will start an immune response, otherwise, they will carry on. The ability to differentiate self from non-self is for that reason a key quality of the body immune system and T cells undergo very selective training, by dendritic cells, to make sure they can make that distinction.
The cells in our body display screen numerous particles on their surface that identify them as “self” to immune cells. Among these self-identifying particles is CD47. It was understood that if T cells lack CD47, they would be effectively eliminated by other immune cells. However, numerous try outs mice doing not have CD47 stopped working to produce an indicator of the molecular mechanism of which cells was accountable for the removal.
When they do not have a surface molecule called CD47, it was known that T cells are killed. Now, a research group at Kobe University has determined the offender and found an unanticipated capability of the immune system that has the potential for cancer treatment. Credit: Professor Nitta Ryo (Graduate School of Medicine, Division of Structural Medicine and Anatomy, Kobe University).
Now, the research group of Associate Professor Saito Yasuyuki, Postdoctoral fellow Komori Satomi, and Specially Appointed Professor Matozaki Takashi at Kobe University, that has been dealing with the molecular interaction between dendritic cells and T cells and in particular on the function of CD47 in that procedure, attempted a novel method. Saito explains: “We created genetically modified mice in which just T cells do not have CD47. This is rather various from the conventional approach with mice that methodically do not have CD47 on all cells.” This new technique enabled them to isolate the function of CD47 on T cells from other aspects that might affect the interaction.
“This result is totally novel since it was thought that CD47-deficient cells are engulfed by a type of immune cells called macrophages and that dendritic cells never cause cell death in other immune cells,” says Saito. The team therefore discovered a totally new method in which the body identifies missing-self cells, that is, cells lacking CD47 being eliminated straight by dendritic cells.
Now that this new ability of dendritic cells has been found, is it utilized on other kinds of cells, too, and can it be used therapeutically? Saito says: “Our results raise the concern: do dendritic cells cause cell death in other cells that lack CD47?
The group has actually already started more research tasks to clarify these questions and also to better understand the system behind this newly-discovered ability of dendritic cells. They have actually likewise started work to validate the potential of dealing with cancer based on this novel finding.
Recommendation: “CD47 promotes peripheral T cell survival by preventing dendritic cell– mediated T cell necroptosis” by Satomi Komori, Yasuyuki Saito, Taichi Nishimura, Datu Respatika, Hiromi Endoh, Hiroki Yoshida, Risa Sugihara, Rie Iida-Norita, Tania Afroj, Tomoko Takai, Okechi S. Oduori, Eriko Nitta, Takenori Kotani, Yoji Murata, Yoriaki Kaneko, Ryo Nitta, Hiroshi Ohnishi and Takashi Matozaki, 7 August 2023, Proceedings of the National Academy of Sciences.DOI: 10.1073/ pnas.2304943120.
The study was funded by the Japan Agency for Medical Research and Development (AMED) Project for Accelerating Next-Generation Cancer Treatment (P-PROMOTE), the Project for Creation of Next-Generation Cancer Treatment (P-CREATE), and the JST Co-creation Opportunity Formation Support Program (COI-NEXT).
Now, the research group of Associate Professor Saito Yasuyuki, Postdoctoral fellow Komori Satomi, and Specially Appointed Professor Matozaki Takashi at Kobe University, that has actually been working on the molecular interaction in between dendritic cells and T cells and in specific on the role of CD47 in that procedure, attempted a novel technique. Their outcomes, released in the journal PNAS, clearly identified dendritic cells as those eliminating T cells doing not have CD47. “This outcome is totally unique due to the fact that it was thought that CD47-deficient cells are engulfed by a type of immune cells called macrophages and that dendritic cells never ever cause cell death in other immune cells,” says Saito. The group thus found an entirely new method in which the body identifies missing-self cells, that is, cells lacking CD47 being eliminated straight by dendritic cells.
Saito states: “Our results raise the question: do dendritic cells cause cell death in other cells that do not have CD47?