The characteristic of trained immunity is that innate immune cells undergo histone modification and metabolic changes after exposure to inflammatory signals, which will lead to an increase in the body's responsiveness to secondary stimulation. Although researchers are now increasingly beginning to understand the molecular regulatory mechanisms behind the body's trained immunity, the key role played by adaptive immune cells is still unclear.
Recently, in a research report entitled "Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling" published in the international journal Cell Reports, scientists from Radboud Medical Center and other institutions found through research that T cells from the adaptive immune system can manipulate the memory of innate immune cells. Previously, researchers believed that the memory of innate immune cells operated independently.
This amazing connection may provide scientists with new possibilities for understanding a variety of human diseases. After studying mouse models, researchers found that if the interaction between the body's T cells and innate immunity is temporarily blocked after organ transplantation, then patients do not need to use immunosuppressive drugs after organ transplantation. The adaptive immune system develops through infections that people experience. This immune response develops more slowly, is highly specific to the pathogen, and uses memory cells to work. In addition, the body's innate immune system also responds much faster to invaders and serves as the first line of defense.
Figure 1. Blocking CD40-TRAF6 signaling inhibits trained immunity in monocytes in vitro. (Jacobs M M E, et al., 2024)
About 10 years ago, scientists discovered that cells in the body's innate system also have memory, allowing them to respond faster and stronger to repeated infections, which is called "trained immunity." Until now, trained immunity was considered a separate process from innate immune cells. However, in this study, the researchers found that T cells from the innate immune system play a crucial role in regulating the body's trained immunity, which may occur through direct contact between CD40 molecules. This research finding may provide new possibilities for treating a variety of human diseases in which trained immunity plays an important role, such as autoimmune diseases, cancer, cardiovascular diseases and organ transplantation. After studying mouse models, they found that when the interaction between T cells and the innate immune system was briefly blocked after transplantation, the transplanted heart could be accepted by the recipient for a long time.
| Cat.No. | Product Name | Price |
|---|---|---|
| CLOE-1193 | Human CD40(Fc) HEK293 Cell Lysate | Inquiry |
| CLOE-2106 | Rat Cd40 (Fc) HEK293 Cell Lysate | Inquiry |
| CLOE-2761 | Mouse Cd40 (Fc) HEK293 Cell Lysate | Inquiry |
| CSC-DC002750 | Panoply™ Human CD40 Knockdown Stable Cell Line | Inquiry |
| CSC-RO0044 | Human CD40 Stable Cell Line-CHO | Inquiry |
| CSC-RO0269 | Human CD40 Stable Cell Line - HEK293T | Inquiry |
| CSC-RO0270 | Human CD40 Stable Cell Line - HT1080 | Inquiry |
| CSC-RO0498 | Monkey CD40 Stable Cell Line - CHO-K1 | Inquiry |
| CSC-RO0536 | Monkey CD40 Stable Cell Line - HEK293T | Inquiry |
| CSC-RO0687 | Mouse CD40 Stable Cell Line - CHO-K1 | Inquiry |
| CSC-RO1060 | Human CD40 Stable Cell Line-Jurkat | Inquiry |
| AD03351Z | Human CD40 adenoviral particles | Inquiry |
| LV08438L | human CD40 (NM_152854) lentivirus particles | Inquiry |
| LV08439L | human CD40 (NM_001250) lentivirus particles | Inquiry |
In this model, the researchers used a combination of nanoparticles and drugs that can inhibit CD40 signaling. One week after the heart transplant, they combined three injections of these nanoparticles with an injection of the current drug CTLA4-Ig, which resulted in the transplanted heart being accepted by the recipient for a long time without the need for other immunosuppressive drugs. In fact, the innate immune system with memory is essential for the body's defense. However, sometimes the innate immune system is in an overactive state, such as in autoimmune diseases, cardiovascular diseases and organ transplantation. And these memories can also have harmful effects, and understanding the molecular mechanisms behind this memory is essential for the development of new therapies.
The researchers believe that manipulating the memory of the innate immune system may potentially serve as a new therapeutic strategy in organ transplantation. In the next few years, the researchers will continue to conduct in-depth research to make this therapy possible in humans. In summary, these research results show that the body's trained immunity can be regulated by CD40-TRAF6 signaling between bone marrow and adaptive immune cells, which may be expected to be used for therapeutic purposes.
Reference
Jacobs M M E, et al. Trained immunity is regulated by T cell-induced CD40-TRAF6 signaling. Cell Reports, 2024, 43(9).