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On January 11, 2022, Hu Xiaoyu's research group from the Institute of Immunology, Tsinghua University published a research paper online in the Journal of Experimental Medicine entitled: CD127 imprints functional heterogeneity to diversify monocyte responses in inflammatory diseases, revealing a group of The high expression of CD127 in monocytes in inflammatory tissues of different diseases, and the anti-inflammatory effects of CD127 and the corresponding IL-7 receptor signaling pathway in monocytes, characterize the functional heterogeneity of human monocytes indicated by CD127 sex
.
Monocytes, as important innate immune cells in the body, mediate the occurrence of inflammatory responses in a variety of disease conditions
.
Existing knowledge of monocytes in the inflammatory response is mostly based on experimental animal models
.
However, phenotypic studies of immune cells in human tissues under disease conditions have revealed inconsistencies in immunophenotypes between humans and experimental mouse models
.
Therefore, exploring the immunophenotype of human monocytes under disease inflammatory conditions is particularly important for understanding the real inflammatory response in vivo
.
At the same time, with the innovation of single-cell analysis technology, the immunophenotype of human monocytes in specific inflammatory tissues has been characterized and correlated with specific disease pathological states, which also raises another important problem.
Does a specific immune microenvironment mediate the adaptation of inflammatory monocytes to the tissue environment while also having a common monocyte immune phenotype? With the above important questions about the immune phenotype of human monocytes, Professor Hu Xiaoyu's research group has carried out collaborative research with research teams from many domestic research institutes
.
CD127(IL7R)+ monocytes/macrophages show a low pro-inflammatory phenotype in the lungs of patients with new coronary pneumonia.
The research team used technical means including tissue sections and single-cell transcript sequencing to detect single cells in a variety of human inflammatory tissues.
Nuclear cells have been studied and found that there are a considerable number of CD127 high-expressing monocytes in the lungs of patients with new crowns and in the peripheral blood and joint tissues of patients with rheumatoid arthritis
.
As the alpha subunit of the IL-7 receptor, CD127 is widely believed to be highly expressed in lymphocytes and mediate important lymphocyte development and viability
.
As atypical CD127-expressing cells, the functions of CD127 and IL-7 receptor signaling on human monocytes are not known until now
.
Using an in vitro model of inflammatory activation, the research team reproduced the high CD127-expressing monocytes observed in vivo and demonstrated that inducible expression of CD127 produced a functional IL-7 receptor on monocytes
.
Even more surprising to the researchers, unsupervised clustering of in vitro activated human monocytes using single-cell transcript analysis revealed that differences in CD127 expression levels among monocyte subsets indicate varying degrees of monocytosis.
The inflammatory phenotype of nuclear cells, that is, the CD127 high expression subgroup shows the low expression of various pro-inflammatory factors
.
Based on the above correlation results, in a subsequent series of functional exploration experiments on CD127 and the low pro-inflammatory phenotype of monocytes, the research team discovered for the first time CD127-STAT5 signaling mediated by IL-7 receptors on monocytes The pathway has an anti-inflammatory regulatory effect, and through the important effector transcription factor STAT5 downstream of CD127, it coordinates the monocyte epigenetic map associated with CD127 expression and realizes the regulation of monocyte inflammatory phenotype
.
In addition, high CD127 expression was shown to indicate a low pro-inflammatory monocyte phenotype in inflammatory tissues of different diseases, which also reflects the commonality of human monocytes in different inflammatory conditions
.
Further, the research team conducted an integrated analysis of single-cell transcriptome data using analysis methods based on machine learning models.
The results showed that the high expression of CD127 indicates a group of monocyte subsets that widely exist in different inflammatory conditions.
Highly uniform specific transcripts were shown in the lungs of patients with Covid-19 and joint tissues of patients with rheumatoid arthritis, as well as under in vitro activation conditions
.
CD127(IL7R)+ monocytes exhibit a low pro-inflammatory phenotype in synovial tissue and peripheral blood of RA patients In conclusion, the work of this thesis has identified CD127-highly expressed monocytes in inflammatory conditions of various diseases Cell subsets, for the first time, the expression of CD127 on monocytes was associated with the low-inflammatory phenotype of monocytes, proving the anti-inflammatory effect of CD127 and its downstream STAT5 signaling pathway in monocytes, thus revealing a A wide range of human monocyte functional heterogeneity indicated by CD127 under different inflammatory conditions
.
It is worth noting that it has been more than ten years since researchers including Professor Hu Xiaoyu observed the inducible expression of CD127 in activated human monocytes in vitro.
This study is the first to demonstrate the induction of CD127 in human monocytes.
Physiological functions expressed
.
At the same time, in this study, it was found that the abundance of CD127 highly expressed monocytes in the lungs of new coronary patients was negatively correlated with the severity of clinical symptoms of patients, suggesting that CD127-mediated monocyte immune phenotype after further research Possibilities as relevant targets for future disease treatments
.
All human tissues and primary human immune cells were used in this study, which is inseparable from the close cooperation and support with multiple clinical and basic teams
.
Prof.
Hu Xiaoyu from the Institute of Immunology, Tsinghua University is the main corresponding author of this paper, Prof.
Zhao Yan from Peking Union Medical College Hospital and Academician Bian Xiuwu from Southwest Hospital of Army Medical University are the co-corresponding authors of this paper, Zhang Bin, a doctoral student at the Institute of Immunology of Tsinghua University, and postdoctoral fellow ( Out of the station) Dr.
Zhang Yuan is the co-first author of the paper
.
The big data integration and analysis has been greatly assisted and supported by Professor Zhang Qiangfeng from the School of Life Sciences of Tsinghua University, and the new crown single-cell omics research has received important support from Professor Zhang Zheng from Shenzhen Third People's Hospital
.
In addition, researchers from Prof.
Hu Xiaoyu's research group from the Institute of Immunology, Tsinghua University, Prof.
Zhao Yan's research group from Peking Union Medical College Hospital, Academician Bian Xiuwu's research group from Army Medical University, and Prof.
Zhang Qiangfeng's research group from School of Life Sciences, Tsinghua University made important contributions to this study.
Contribute
.
The research was funded by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chongqing Municipal Health Commission, the Spring Breeze Fund of Tsinghua University, the Tsinghua University-Peking University Life Science Joint Center, and the Institute of Immunology of Tsinghua University
.
Finally, all the authors would like to express their sincere gratitude to the patients and their families who provided samples for this study.
Although some patients are no longer alive, we believe that their dedication and contribution to immunological research will benefit people suffering from inflammatory diseases in the future
.
Paper link: https://doi.
org/10.
1084/jem.
20211191 Open for reprinting, welcome to forward to Moments and WeChat groups
.
Monocytes, as important innate immune cells in the body, mediate the occurrence of inflammatory responses in a variety of disease conditions
.
Existing knowledge of monocytes in the inflammatory response is mostly based on experimental animal models
.
However, phenotypic studies of immune cells in human tissues under disease conditions have revealed inconsistencies in immunophenotypes between humans and experimental mouse models
.
Therefore, exploring the immunophenotype of human monocytes under disease inflammatory conditions is particularly important for understanding the real inflammatory response in vivo
.
At the same time, with the innovation of single-cell analysis technology, the immunophenotype of human monocytes in specific inflammatory tissues has been characterized and correlated with specific disease pathological states, which also raises another important problem.
Does a specific immune microenvironment mediate the adaptation of inflammatory monocytes to the tissue environment while also having a common monocyte immune phenotype? With the above important questions about the immune phenotype of human monocytes, Professor Hu Xiaoyu's research group has carried out collaborative research with research teams from many domestic research institutes
.
CD127(IL7R)+ monocytes/macrophages show a low pro-inflammatory phenotype in the lungs of patients with new coronary pneumonia.
The research team used technical means including tissue sections and single-cell transcript sequencing to detect single cells in a variety of human inflammatory tissues.
Nuclear cells have been studied and found that there are a considerable number of CD127 high-expressing monocytes in the lungs of patients with new crowns and in the peripheral blood and joint tissues of patients with rheumatoid arthritis
.
As the alpha subunit of the IL-7 receptor, CD127 is widely believed to be highly expressed in lymphocytes and mediate important lymphocyte development and viability
.
As atypical CD127-expressing cells, the functions of CD127 and IL-7 receptor signaling on human monocytes are not known until now
.
Using an in vitro model of inflammatory activation, the research team reproduced the high CD127-expressing monocytes observed in vivo and demonstrated that inducible expression of CD127 produced a functional IL-7 receptor on monocytes
.
Even more surprising to the researchers, unsupervised clustering of in vitro activated human monocytes using single-cell transcript analysis revealed that differences in CD127 expression levels among monocyte subsets indicate varying degrees of monocytosis.
The inflammatory phenotype of nuclear cells, that is, the CD127 high expression subgroup shows the low expression of various pro-inflammatory factors
.
Based on the above correlation results, in a subsequent series of functional exploration experiments on CD127 and the low pro-inflammatory phenotype of monocytes, the research team discovered for the first time CD127-STAT5 signaling mediated by IL-7 receptors on monocytes The pathway has an anti-inflammatory regulatory effect, and through the important effector transcription factor STAT5 downstream of CD127, it coordinates the monocyte epigenetic map associated with CD127 expression and realizes the regulation of monocyte inflammatory phenotype
.
In addition, high CD127 expression was shown to indicate a low pro-inflammatory monocyte phenotype in inflammatory tissues of different diseases, which also reflects the commonality of human monocytes in different inflammatory conditions
.
Further, the research team conducted an integrated analysis of single-cell transcriptome data using analysis methods based on machine learning models.
The results showed that the high expression of CD127 indicates a group of monocyte subsets that widely exist in different inflammatory conditions.
Highly uniform specific transcripts were shown in the lungs of patients with Covid-19 and joint tissues of patients with rheumatoid arthritis, as well as under in vitro activation conditions
.
CD127(IL7R)+ monocytes exhibit a low pro-inflammatory phenotype in synovial tissue and peripheral blood of RA patients In conclusion, the work of this thesis has identified CD127-highly expressed monocytes in inflammatory conditions of various diseases Cell subsets, for the first time, the expression of CD127 on monocytes was associated with the low-inflammatory phenotype of monocytes, proving the anti-inflammatory effect of CD127 and its downstream STAT5 signaling pathway in monocytes, thus revealing a A wide range of human monocyte functional heterogeneity indicated by CD127 under different inflammatory conditions
.
It is worth noting that it has been more than ten years since researchers including Professor Hu Xiaoyu observed the inducible expression of CD127 in activated human monocytes in vitro.
This study is the first to demonstrate the induction of CD127 in human monocytes.
Physiological functions expressed
.
At the same time, in this study, it was found that the abundance of CD127 highly expressed monocytes in the lungs of new coronary patients was negatively correlated with the severity of clinical symptoms of patients, suggesting that CD127-mediated monocyte immune phenotype after further research Possibilities as relevant targets for future disease treatments
.
All human tissues and primary human immune cells were used in this study, which is inseparable from the close cooperation and support with multiple clinical and basic teams
.
Prof.
Hu Xiaoyu from the Institute of Immunology, Tsinghua University is the main corresponding author of this paper, Prof.
Zhao Yan from Peking Union Medical College Hospital and Academician Bian Xiuwu from Southwest Hospital of Army Medical University are the co-corresponding authors of this paper, Zhang Bin, a doctoral student at the Institute of Immunology of Tsinghua University, and postdoctoral fellow ( Out of the station) Dr.
Zhang Yuan is the co-first author of the paper
.
The big data integration and analysis has been greatly assisted and supported by Professor Zhang Qiangfeng from the School of Life Sciences of Tsinghua University, and the new crown single-cell omics research has received important support from Professor Zhang Zheng from Shenzhen Third People's Hospital
.
In addition, researchers from Prof.
Hu Xiaoyu's research group from the Institute of Immunology, Tsinghua University, Prof.
Zhao Yan's research group from Peking Union Medical College Hospital, Academician Bian Xiuwu's research group from Army Medical University, and Prof.
Zhang Qiangfeng's research group from School of Life Sciences, Tsinghua University made important contributions to this study.
Contribute
.
The research was funded by the National Natural Science Foundation of China, the Ministry of Science and Technology, the Chongqing Municipal Health Commission, the Spring Breeze Fund of Tsinghua University, the Tsinghua University-Peking University Life Science Joint Center, and the Institute of Immunology of Tsinghua University
.
Finally, all the authors would like to express their sincere gratitude to the patients and their families who provided samples for this study.
Although some patients are no longer alive, we believe that their dedication and contribution to immunological research will benefit people suffering from inflammatory diseases in the future
.
Paper link: https://doi.
org/10.
1084/jem.
20211191 Open for reprinting, welcome to forward to Moments and WeChat groups
