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The new academician column of Science China Life Sciences (FROM CAS & CAE MEMBERS) recently published a research article titled "Pathogen-associated T follicular helper cell plasticity is critical in anti-viral immunity" by the research group of Academician Dong Chen from the Institute of Immunology, Tsinghua University.
.
This article systematically analyzes the plasticity of follicular helper T cells derived from different immune responses, and focuses on the developmental mechanism and important functions of a group of Tfh cells expressing IFN-γ specifically induced by influenza virus in antiviral humoral immune responses.
.
In the process of the body's defense against foreign pathogens, B cells and the antibodies they produce are important means of eliminating pathogenic microorganisms
.
In response to different types of pathogenic microorganisms, B cells can produce different types of antibody subtypes in order to eliminate pathogenic microorganisms in a targeted manner
.
T follicular helper (Tfh) cells are a type of helper T cells that specifically assist in the differentiation and development of B cells, which are essential for B cell follicular germinal center responses and the production of high-affinity antibodies
.
However, in this process, the mechanism by which Tfh cells regulate the production of different subtypes of antibodies is still unclear
.
Previous studies have shown that Tfh cells have different plasticity in different types of immune responses.
However, due to the lack of suitable genetic methods, the characteristics and regulatory mechanisms of their plasticity have not been systematically explored
.
In this study, Dong Chen's group conducted a systematic transcriptome sequencing analysis of Tfh cells developed from different immune responses by high-throughput sequencing technology, and found that Tfh cells respond to different types of immune responses.
Similar transcriptomic signatures of effector helper T cells
.
At the same time, Dong Chen's team paid attention to the specific generation of a group of Tfh cells expressing IFN-γ during influenza virus infection, and found that the generation of this group of Tfh cell subsets depends on the IL-12 signaling pathway
.
By analyzing the cell lineage tracing mouse model, Dong Chen's team found that Tfh cells expressing IFN-γ have a distinct differentiation pathway from IFN-γ-negative Tfh cells during influenza virus infection
.
The specific knockout of IFN-γ-positive Tfh cells by conditional gene knockout proved that this group of cells is crucial for the production of virus-specific antibodies, especially the secretion of IgG2c subtype antibodies, and the deletion of this group of cells will lead to Influenza virus-neutralizing antibodies decreased, suggesting that they play a key role in the defense against influenza virus in mice
.
Tfh cells show corresponding transcriptome characteristics in response to different types of immune responses.
In this study, Dong Chen's group also found that inactivated influenza virus vaccine injection could not well induce the production of IFN-γ-positive Tfh cell subsets , and therefore may affect its clinical protection
.
The above results indicate that the generation of pathogen-specific Tfh cell subsets, and their plasticity, play an important regulatory role in the induction of protective high-affinity antibody subtype switching.
ideas and clues
.
Feng Han, a doctoral student at the Institute of Immunology of Tsinghua University, is the first author of this article, and Academician Dong Chen, PI 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 project include Dr.
Jenny Xie from Pos-Myers Squibb and Professor Tang Hong from the Pasteur Institute, Shanghai, Chinese Academy of Sciences
.
The research was supported by several projects from the National Natural Science Foundation of China, the Beijing Municipal Science and Technology Commission, the Shanghai Municipal Science and Technology Commission, and the Tsinghua University-Peking University Life Joint Center
.
About the author Dong Chen Dong Chen is currently the dean of the Shanghai Institute of Immunotherapy Innovation, a professor of Shanghai Jiaotong University School of Medicine, a professor of Tsinghua University School of Medicine, and a PI of the Institute of Immunology of Tsinghua University
.
Dong Chen graduated from Wuhan University in 1985 with a bachelor's degree, and received his Ph.
D.
from the University of Alabama at Birmingham in 1996.
From 1997 to 2000, he worked as a postdoctoral fellow in the Department of Immunology at Yale University
.
He was a tenured professor and director of the Center for Inflammation and Oncology at the University of Texas MD Anderson Cancer Center, Department of Immunology
.
He returned to work in China in 2013 and served as the director of the Institute of Immunology of Tsinghua University and the dean of the School of Medicine of Tsinghua University
.
Dean Dong Chen is mainly devoted to the research of immunology, and has made a number of pioneering contributions in the field of T cell differentiation and autoimmune diseases.
ideas
.
Dean Dong Chen has published more than 260 papers, and the total number of citations has reached more than 32,000 times
.
Dong Chen is a member of the American Association for the Advancement of Science, an academician of the Chinese Academy of Sciences, and a member of the Chinese Academy of Medical Sciences.
He has won the 2009 American Society of Immunologists BD Bioscience Investigator Award and the 2019 International Cytokine and Interferon Association Biolegend-William E.
Paul Award He was also awarded the Wu Jieping Medical Innovation Award, Wu Yang Medical Award,
etc.
He is the project leader of the National Key R&D Precision Medicine Program, and the leader of the "Inflammatory Biology and Diseases" innovation group of the Fund Committee
.
He is currently the editor-in-chief of Frontiers in Immunology·T Cell Biology, associate editor of Science in China: Life Sciences, Current Opinion in Immunology and Advances in Immunology, editorial board member or scientific advisor of journals such as Annual Review in Immunology, Immunity, Med and Cell Research
.
For details, please read the original text▼[Click the link below or read the original text]Feng, H.
, Zhao,X.
, Xie, J.
, Bai, X.
, Fu, W.
, Chen, H.
, Tang, H.
, Wang , X.
, and Dong, C.
(2022).
Pathogen-associated T follicular helper cell plasticity is critical in anti-viral immunity.
Sci China Life Sci 65, https://doi.
org/10.
1007/s11427-021-2055 -x
.
This article systematically analyzes the plasticity of follicular helper T cells derived from different immune responses, and focuses on the developmental mechanism and important functions of a group of Tfh cells expressing IFN-γ specifically induced by influenza virus in antiviral humoral immune responses.
.
In the process of the body's defense against foreign pathogens, B cells and the antibodies they produce are important means of eliminating pathogenic microorganisms
.
In response to different types of pathogenic microorganisms, B cells can produce different types of antibody subtypes in order to eliminate pathogenic microorganisms in a targeted manner
.
T follicular helper (Tfh) cells are a type of helper T cells that specifically assist in the differentiation and development of B cells, which are essential for B cell follicular germinal center responses and the production of high-affinity antibodies
.
However, in this process, the mechanism by which Tfh cells regulate the production of different subtypes of antibodies is still unclear
.
Previous studies have shown that Tfh cells have different plasticity in different types of immune responses.
However, due to the lack of suitable genetic methods, the characteristics and regulatory mechanisms of their plasticity have not been systematically explored
.
In this study, Dong Chen's group conducted a systematic transcriptome sequencing analysis of Tfh cells developed from different immune responses by high-throughput sequencing technology, and found that Tfh cells respond to different types of immune responses.
Similar transcriptomic signatures of effector helper T cells
.
At the same time, Dong Chen's team paid attention to the specific generation of a group of Tfh cells expressing IFN-γ during influenza virus infection, and found that the generation of this group of Tfh cell subsets depends on the IL-12 signaling pathway
.
By analyzing the cell lineage tracing mouse model, Dong Chen's team found that Tfh cells expressing IFN-γ have a distinct differentiation pathway from IFN-γ-negative Tfh cells during influenza virus infection
.
The specific knockout of IFN-γ-positive Tfh cells by conditional gene knockout proved that this group of cells is crucial for the production of virus-specific antibodies, especially the secretion of IgG2c subtype antibodies, and the deletion of this group of cells will lead to Influenza virus-neutralizing antibodies decreased, suggesting that they play a key role in the defense against influenza virus in mice
.
Tfh cells show corresponding transcriptome characteristics in response to different types of immune responses.
In this study, Dong Chen's group also found that inactivated influenza virus vaccine injection could not well induce the production of IFN-γ-positive Tfh cell subsets , and therefore may affect its clinical protection
.
The above results indicate that the generation of pathogen-specific Tfh cell subsets, and their plasticity, play an important regulatory role in the induction of protective high-affinity antibody subtype switching.
ideas and clues
.
Feng Han, a doctoral student at the Institute of Immunology of Tsinghua University, is the first author of this article, and Academician Dong Chen, PI 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 project include Dr.
Jenny Xie from Pos-Myers Squibb and Professor Tang Hong from the Pasteur Institute, Shanghai, Chinese Academy of Sciences
.
The research was supported by several projects from the National Natural Science Foundation of China, the Beijing Municipal Science and Technology Commission, the Shanghai Municipal Science and Technology Commission, and the Tsinghua University-Peking University Life Joint Center
.
About the author Dong Chen Dong Chen is currently the dean of the Shanghai Institute of Immunotherapy Innovation, a professor of Shanghai Jiaotong University School of Medicine, a professor of Tsinghua University School of Medicine, and a PI of the Institute of Immunology of Tsinghua University
.
Dong Chen graduated from Wuhan University in 1985 with a bachelor's degree, and received his Ph.
D.
from the University of Alabama at Birmingham in 1996.
From 1997 to 2000, he worked as a postdoctoral fellow in the Department of Immunology at Yale University
.
He was a tenured professor and director of the Center for Inflammation and Oncology at the University of Texas MD Anderson Cancer Center, Department of Immunology
.
He returned to work in China in 2013 and served as the director of the Institute of Immunology of Tsinghua University and the dean of the School of Medicine of Tsinghua University
.
Dean Dong Chen is mainly devoted to the research of immunology, and has made a number of pioneering contributions in the field of T cell differentiation and autoimmune diseases.
ideas
.
Dean Dong Chen has published more than 260 papers, and the total number of citations has reached more than 32,000 times
.
Dong Chen is a member of the American Association for the Advancement of Science, an academician of the Chinese Academy of Sciences, and a member of the Chinese Academy of Medical Sciences.
He has won the 2009 American Society of Immunologists BD Bioscience Investigator Award and the 2019 International Cytokine and Interferon Association Biolegend-William E.
Paul Award He was also awarded the Wu Jieping Medical Innovation Award, Wu Yang Medical Award,
etc.
He is the project leader of the National Key R&D Precision Medicine Program, and the leader of the "Inflammatory Biology and Diseases" innovation group of the Fund Committee
.
He is currently the editor-in-chief of Frontiers in Immunology·T Cell Biology, associate editor of Science in China: Life Sciences, Current Opinion in Immunology and Advances in Immunology, editorial board member or scientific advisor of journals such as Annual Review in Immunology, Immunity, Med and Cell Research
.
For details, please read the original text▼[Click the link below or read the original text]Feng, H.
, Zhao,X.
, Xie, J.
, Bai, X.
, Fu, W.
, Chen, H.
, Tang, H.
, Wang , X.
, and Dong, C.
(2022).
Pathogen-associated T follicular helper cell plasticity is critical in anti-viral immunity.
Sci China Life Sci 65, https://doi.
org/10.
1007/s11427-021-2055 -x
