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Editor-in-Chief | Conventional dendritic cells (DC), as the main antigen-presenting cells, are essential for initiating adaptive immunity
.
The spleen is the largest immune organ in the body.
It has a unique open blood circulatory system and is the center of the body's humoral and cellular immunity
.
Type 2 dendritic cells (type 2 conventional dendritic cells, cDC2), as a DC subset in the spleen, are mainly located in the bridging channel (BC)
.
The BC is located between the white pulp and the red pulp and is an area full of open blood circulation and shear forces
.
Thus, cDC2s distributed in BCs are more efficient at capturing antigens from the blood and presenting them to T cells, but the mechanism of how cDC2s sense their environment and maintain homeostasis in a blood-filled environment is not entirely clear.
Not sure
.
On February 11, 2022, the team of Jason G.
Cyster at the University of California, San Francisco (first authors are Dan Liu and Dan Liu) published a research paper CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells in the journal Science, revealing that The role of CD97 in maintaining dendritic cell homeostasis in the spleen by mechanosensing red blood cells
.
Through in vivo CRISPR-based screening combined with animal models, the researchers found that deletion of the CD97-Ga13-Arhgef1 pathway resulted in the loss of cDC2 in the spleen, but had no effect on type 1 conventional dendritic cells (cDC1)
.
Using two-photon microscopic intravital imaging and spleen transplantation experiments, the researchers demonstrated that cDC2s lacking the CD97-Ga13-Arhgef1 pathway in the spleen are more mobile and more likely to be lost into the bloodstream, and can be detected in peripheral blood.
to more cDC2
.
As a member of adhesion G protein-coupled receptors (adhesion G protein-coupled receptors, adhesion GPCRs), CD97 possesses a complex multi-domain NTF (N-terminal fragment) and a highly conserved domain GPCR-proteolytic that can be hydrolyzed site (GPS)
.
After autocatalytic hydrolysis, the NTF, the transmembrane domain and the CTF (C-terminal fragment) are all non-covalently coupled together
.
Through experiments such as antibody blocking and knockout mice, the researchers found that CD55, as a ligand for CD97, played the same role in maintaining cDC2 homeostasis in the spleen
.
However, cDC2 itself does not express CD55, but red blood cells express a large amount of CD55, and the homeostasis of cDC2 in the spleen can be restored to some extent by reinfusion of wild-type red blood cells in CD55-deficient mice
.
This process requires the presence of shearing force, so that the NTF of CD97 is removed, thereby stimulating the GPCR and downstream molecules
.
And when the mutant incapable of autocatalytic hydrolysis was overexpressed in CD97-deficient cells, the depletion of cDC2 cells in the spleen caused by CD97 deletion was also not restored
.
Past studies have shown that the transcription factor IRF4 is essential for the maintenance of cDC2 homeostasis
.
Combined with the ChIPseq database and RNAseq analysis, the researchers found that IRF4 regulates the expression of CD97 on cDC2, and overexpression of CD97 in IRF4-deficient cells can partially restore the homeostasis of cDC2 in the spleen, so this data suggests that IRF4 is partially mediated by The expression of CD97 is maintained to regulate cDC2
.
Finally, loss of the CD55-CD97-Ga13-Arhgef1 pathway affects cDC2 endocytosis, thereby impairing antigen presentation, affecting T cell differentiation and germinal center formation
.
Collectively, this study reveals a novel mechanism by which a novel GPCR promotes the function and maintenance of cDC2 in the spleen.
That is, cDC2 mechanosenses CD55 on red blood cells through CD97 and activates Ga13 signaling by removing NTF by shear force.
The pathway keeps cells from being lost in the blood circulation
.
This will broaden our knowledge of mechanosensitive molecular systems and adhesion GPCR families, and will help to further explore the potential therapeutic value of such families
.
Original link: https://doi.
org/10.
1126/science.
abi5965 Publisher: 11 Reprint Notice [Non-original article] The copyright of this article belongs to the author of the article.
Personal reposting and sharing are welcome.
Reprinting is prohibited without permission.
The author owns all legal rights, and violators will be prosecuted
.
.
The spleen is the largest immune organ in the body.
It has a unique open blood circulatory system and is the center of the body's humoral and cellular immunity
.
Type 2 dendritic cells (type 2 conventional dendritic cells, cDC2), as a DC subset in the spleen, are mainly located in the bridging channel (BC)
.
The BC is located between the white pulp and the red pulp and is an area full of open blood circulation and shear forces
.
Thus, cDC2s distributed in BCs are more efficient at capturing antigens from the blood and presenting them to T cells, but the mechanism of how cDC2s sense their environment and maintain homeostasis in a blood-filled environment is not entirely clear.
Not sure
.
On February 11, 2022, the team of Jason G.
Cyster at the University of California, San Francisco (first authors are Dan Liu and Dan Liu) published a research paper CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells in the journal Science, revealing that The role of CD97 in maintaining dendritic cell homeostasis in the spleen by mechanosensing red blood cells
.
Through in vivo CRISPR-based screening combined with animal models, the researchers found that deletion of the CD97-Ga13-Arhgef1 pathway resulted in the loss of cDC2 in the spleen, but had no effect on type 1 conventional dendritic cells (cDC1)
.
Using two-photon microscopic intravital imaging and spleen transplantation experiments, the researchers demonstrated that cDC2s lacking the CD97-Ga13-Arhgef1 pathway in the spleen are more mobile and more likely to be lost into the bloodstream, and can be detected in peripheral blood.
to more cDC2
.
As a member of adhesion G protein-coupled receptors (adhesion G protein-coupled receptors, adhesion GPCRs), CD97 possesses a complex multi-domain NTF (N-terminal fragment) and a highly conserved domain GPCR-proteolytic that can be hydrolyzed site (GPS)
.
After autocatalytic hydrolysis, the NTF, the transmembrane domain and the CTF (C-terminal fragment) are all non-covalently coupled together
.
Through experiments such as antibody blocking and knockout mice, the researchers found that CD55, as a ligand for CD97, played the same role in maintaining cDC2 homeostasis in the spleen
.
However, cDC2 itself does not express CD55, but red blood cells express a large amount of CD55, and the homeostasis of cDC2 in the spleen can be restored to some extent by reinfusion of wild-type red blood cells in CD55-deficient mice
.
This process requires the presence of shearing force, so that the NTF of CD97 is removed, thereby stimulating the GPCR and downstream molecules
.
And when the mutant incapable of autocatalytic hydrolysis was overexpressed in CD97-deficient cells, the depletion of cDC2 cells in the spleen caused by CD97 deletion was also not restored
.
Past studies have shown that the transcription factor IRF4 is essential for the maintenance of cDC2 homeostasis
.
Combined with the ChIPseq database and RNAseq analysis, the researchers found that IRF4 regulates the expression of CD97 on cDC2, and overexpression of CD97 in IRF4-deficient cells can partially restore the homeostasis of cDC2 in the spleen, so this data suggests that IRF4 is partially mediated by The expression of CD97 is maintained to regulate cDC2
.
Finally, loss of the CD55-CD97-Ga13-Arhgef1 pathway affects cDC2 endocytosis, thereby impairing antigen presentation, affecting T cell differentiation and germinal center formation
.
Collectively, this study reveals a novel mechanism by which a novel GPCR promotes the function and maintenance of cDC2 in the spleen.
That is, cDC2 mechanosenses CD55 on red blood cells through CD97 and activates Ga13 signaling by removing NTF by shear force.
The pathway keeps cells from being lost in the blood circulation
.
This will broaden our knowledge of mechanosensitive molecular systems and adhesion GPCR families, and will help to further explore the potential therapeutic value of such families
.
Original link: https://doi.
org/10.
1126/science.
abi5965 Publisher: 11 Reprint Notice [Non-original article] The copyright of this article belongs to the author of the article.
Personal reposting and sharing are welcome.
Reprinting is prohibited without permission.
The author owns all legal rights, and violators will be prosecuted
.
