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In humoral immunity, T cells provide B cells with help in many aspects, such as survival, proliferation, class switching, and affinity maturation
.
Earlier studies found a group of CD4+ helper T cells that are located in B cell follicles and express the chemokine receptor CXCR5, that is, follicular helper T (Tfh) cells are indispensable for the normal function of B cells; later from Dong Chen Research in other laboratories identified Bcl6 as its lineage-specific transcription factor
.
Therefore, Tfh cells have also been shown to be an independent subset of helper T cells
.
Since its discovery, our understanding of Tfh cells has made considerable progress; however, we have not yet fully understood the differentiation process
.
On October 12, 2021, the team of Professor Dong Chen from the Institute of Immunology of Tsinghua University published an online research paper entitled Costimulation molecules differentially regulate the ERK-Zfp831 axis to shape T follicular helper cell differentiation in Immunity.
The stimulating molecule-ERK-Zfp831 axis plays an important role in regulating the differentiation of follicular helper T (Tfh) cells
.
In this topic, researchers from Dong Chen's team first established a method for effectively inducing Tfh-like cells in vitro
.
Interestingly, the activation of the ERK pathway was weakened under this induction condition
.
Further studies have found that inhibition of the ERK pathway enhances the differentiation of Tfh cells in vitro and in vivo
.
The ERK pathway is activated by multiple receptors
.
Researchers first used an in vitro culture system and found that the costimulatory molecule CD28 maintained the activation of ERK in T cells for a long period of time
.
ICOS and CD28 are both costimulatory molecules and have strong homology
.
ICOS is indispensable to the differentiation process of Tfh cells
.
But compared to CD28, ICOS lacks the ability to activate ERK
.
The researchers further discovered that it is precisely because ICOS does not have the ability to activate ERK, so that it can maintain the differentiation of Tfh cells
.
On the contrary, if ICOS has the ability to activate ERK, it will cause obvious damage to the differentiation of Tfh cells
.
The researchers then identified Zfp831 as a transcription factor suppressed by the ERK pathway, which promotes Tfh cell differentiation by directly up-regulating the expression of Bcl6 and Tcf7
.
At the same time, it also promotes its differentiation indirectly by inhibiting a large number of genes that have a negative effect on the differentiation of Tfh cells
.
By comparing with the other two key transcription factors Bcl6 and Ascl2 in the differentiation process of Tfh cells, the researchers found that the transcriptional regulatory network led by Zfp831 is independent of the former two
.
At the same time, Hivep2 played a compensation role when Zfp831 was knocked out
.
The costimulatory molecule-ERK-Zfp831 axis regulates the differentiation of Tfh cells.
So far, researchers have discovered that the ERK-Zfp831 axis, which is regulated by costimulatory signals, plays a key role in the regulation of Tfh cell development
.
The research results provide theoretical support and reference operating methods for manipulating Tfh cell differentiation in vivo to enhance or weaken humoral immunity
.
Wan Siyuan, a doctoral student of the Institute of Immunology of Tsinghua University, is the first author of this article, and Academician Dong Chen, professor of the Institute of Immunology of Tsinghua University and dean of the Shanghai Institute of Immunotherapy Innovation, is the corresponding author of this article
.
The collaborators on this subject include Professor Liu Xindong from the Southwest Hospital of the Army Military Medical University
.
Original link: https:// Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission , The author has all legal rights, and offenders must be investigated
.
.
Earlier studies found a group of CD4+ helper T cells that are located in B cell follicles and express the chemokine receptor CXCR5, that is, follicular helper T (Tfh) cells are indispensable for the normal function of B cells; later from Dong Chen Research in other laboratories identified Bcl6 as its lineage-specific transcription factor
.
Therefore, Tfh cells have also been shown to be an independent subset of helper T cells
.
Since its discovery, our understanding of Tfh cells has made considerable progress; however, we have not yet fully understood the differentiation process
.
On October 12, 2021, the team of Professor Dong Chen from the Institute of Immunology of Tsinghua University published an online research paper entitled Costimulation molecules differentially regulate the ERK-Zfp831 axis to shape T follicular helper cell differentiation in Immunity.
The stimulating molecule-ERK-Zfp831 axis plays an important role in regulating the differentiation of follicular helper T (Tfh) cells
.
In this topic, researchers from Dong Chen's team first established a method for effectively inducing Tfh-like cells in vitro
.
Interestingly, the activation of the ERK pathway was weakened under this induction condition
.
Further studies have found that inhibition of the ERK pathway enhances the differentiation of Tfh cells in vitro and in vivo
.
The ERK pathway is activated by multiple receptors
.
Researchers first used an in vitro culture system and found that the costimulatory molecule CD28 maintained the activation of ERK in T cells for a long period of time
.
ICOS and CD28 are both costimulatory molecules and have strong homology
.
ICOS is indispensable to the differentiation process of Tfh cells
.
But compared to CD28, ICOS lacks the ability to activate ERK
.
The researchers further discovered that it is precisely because ICOS does not have the ability to activate ERK, so that it can maintain the differentiation of Tfh cells
.
On the contrary, if ICOS has the ability to activate ERK, it will cause obvious damage to the differentiation of Tfh cells
.
The researchers then identified Zfp831 as a transcription factor suppressed by the ERK pathway, which promotes Tfh cell differentiation by directly up-regulating the expression of Bcl6 and Tcf7
.
At the same time, it also promotes its differentiation indirectly by inhibiting a large number of genes that have a negative effect on the differentiation of Tfh cells
.
By comparing with the other two key transcription factors Bcl6 and Ascl2 in the differentiation process of Tfh cells, the researchers found that the transcriptional regulatory network led by Zfp831 is independent of the former two
.
At the same time, Hivep2 played a compensation role when Zfp831 was knocked out
.
The costimulatory molecule-ERK-Zfp831 axis regulates the differentiation of Tfh cells.
So far, researchers have discovered that the ERK-Zfp831 axis, which is regulated by costimulatory signals, plays a key role in the regulation of Tfh cell development
.
The research results provide theoretical support and reference operating methods for manipulating Tfh cell differentiation in vivo to enhance or weaken humoral immunity
.
Wan Siyuan, a doctoral student of the Institute of Immunology of Tsinghua University, is the first author of this article, and Academician Dong Chen, professor of the Institute of Immunology of Tsinghua University and dean of the Shanghai Institute of Immunotherapy Innovation, is the corresponding author of this article
.
The collaborators on this subject include Professor Liu Xindong from the Southwest Hospital of the Army Military Medical University
.
Original link: https:// Reprinting instructions [Non-original article] The copyright of this article belongs to the author of the article.
Personal forwarding and sharing are welcome.
Reprinting is prohibited without permission , The author has all legal rights, and offenders must be investigated
.
