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▎Editor of WuXi AppTec's content team The top academic journal "Nature" recently published a new study online from the research group of Chi Hongbo at St.
Jude Children's Research Hospital
.
Scientists have revealed a new biological pathway that regulates the adaptive immune system
.
The discovery of this mechanism can help develop new drugs, improve the effectiveness of various vaccines, or alleviate autoimmune diseases
.
This research focuses on a type of immune cell called T follicular helper cells (Tfh)
.
The important function of these immune cells is to help activate humoral immunity in the adaptive immune system
.
When the body is infected by foreign bacteria, viruses, etc.
, the adaptive immune system can learn to recognize the intruder and launch an attack
.
Among them, the part of humoral immunity mainly works through the production of antibodies
.
In this study, Professor Chi Hongbo and colleagues used CRISPR-Cas9 technology to screen in mice to find out which key enzymes in the metabolic control pathway will affect the function of Tfh cells after the deletion
.
Experiments have shown that the key component of the cytidine diphosphate (CDP)-ethanolamine metabolic pathway can specifically regulate the post-transcriptional differentiation of Tfh cells and activate Tfh cells
.
And these activated Tfh cells will play their role in assisting the maturation of B cells, thereby prompting B cells to produce antibodies to resist invading viruses
.
"This discovery is very surprising," said Professor Chi Hongbo.
"First of all, this metabolic pathway is believed to have a basic metabolic regulation function and is responsible for the synthesis of cell membrane components.
However, we have discovered one of its main signal transduction functions.
.
Secondly, to our surprise, in a similar metabolic pathway, which is the only way to participate in Tfh regulation
.
"▲ the study corresponding author Professor Chi Hongbo (source: reference [2]) in the experiment, The staff deleted every key enzyme they identified in the CDP-ethanolamine pathway, and found that once these enzymes were missing, they would only specifically affect the development of Tfh cells, but would not damage the overall immune function
.
Therefore, the researchers believe that these key enzymes can be used as drug targets to regulate the activity of T cells by enhancing or inhibiting this pathway
.
Talking about the application of this discovery, Professor Chi Hongbo believes that it will help both the development of vaccines and the treatment of autoimmune diseases
.
"We are exploring whether we can use drugs to activate this pathway to help these T cells mobilize the immune system to produce antibodies, so as to improve the effectiveness of the vaccine
.
" Professor Chi Hongbo said, "On the other hand, we are very interested in the development of inhibition of this.
A new method of pathway to treat autoimmune diseases
.
Because we know that the activation or inhibition of Tfh cells can be highly specific and will not affect other immune functions
.
”Reference materials: [1] Fu,G.
, Guy, CS, Chapman, NM et al.
Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine.
Nature (2021).
https://doi.
org/10.
1038/s41586- 021-03692-z[2] Discovery shows how tuning the immune system may enhance vaccines and ease disease Retrieved July 8, 2021 from https:// news/discovery-shows-how-tuning-the-immune-system-may-enhance-vaccines-and-ease-disease.
html
Jude Children's Research Hospital
.
Scientists have revealed a new biological pathway that regulates the adaptive immune system
.
The discovery of this mechanism can help develop new drugs, improve the effectiveness of various vaccines, or alleviate autoimmune diseases
.
This research focuses on a type of immune cell called T follicular helper cells (Tfh)
.
The important function of these immune cells is to help activate humoral immunity in the adaptive immune system
.
When the body is infected by foreign bacteria, viruses, etc.
, the adaptive immune system can learn to recognize the intruder and launch an attack
.
Among them, the part of humoral immunity mainly works through the production of antibodies
.
In this study, Professor Chi Hongbo and colleagues used CRISPR-Cas9 technology to screen in mice to find out which key enzymes in the metabolic control pathway will affect the function of Tfh cells after the deletion
.
Experiments have shown that the key component of the cytidine diphosphate (CDP)-ethanolamine metabolic pathway can specifically regulate the post-transcriptional differentiation of Tfh cells and activate Tfh cells
.
And these activated Tfh cells will play their role in assisting the maturation of B cells, thereby prompting B cells to produce antibodies to resist invading viruses
.
"This discovery is very surprising," said Professor Chi Hongbo.
"First of all, this metabolic pathway is believed to have a basic metabolic regulation function and is responsible for the synthesis of cell membrane components.
However, we have discovered one of its main signal transduction functions.
.
Secondly, to our surprise, in a similar metabolic pathway, which is the only way to participate in Tfh regulation
.
"▲ the study corresponding author Professor Chi Hongbo (source: reference [2]) in the experiment, The staff deleted every key enzyme they identified in the CDP-ethanolamine pathway, and found that once these enzymes were missing, they would only specifically affect the development of Tfh cells, but would not damage the overall immune function
.
Therefore, the researchers believe that these key enzymes can be used as drug targets to regulate the activity of T cells by enhancing or inhibiting this pathway
.
Talking about the application of this discovery, Professor Chi Hongbo believes that it will help both the development of vaccines and the treatment of autoimmune diseases
.
"We are exploring whether we can use drugs to activate this pathway to help these T cells mobilize the immune system to produce antibodies, so as to improve the effectiveness of the vaccine
.
" Professor Chi Hongbo said, "On the other hand, we are very interested in the development of inhibition of this.
A new method of pathway to treat autoimmune diseases
.
Because we know that the activation or inhibition of Tfh cells can be highly specific and will not affect other immune functions
.
”Reference materials: [1] Fu,G.
, Guy, CS, Chapman, NM et al.
Metabolic control of TFH cells and humoral immunity by phosphatidylethanolamine.
Nature (2021).
https://doi.
org/10.
1038/s41586- 021-03692-z[2] Discovery shows how tuning the immune system may enhance vaccines and ease disease Retrieved July 8, 2021 from https:// news/discovery-shows-how-tuning-the-immune-system-may-enhance-vaccines-and-ease-disease.
html
