Master of Immunization: A Complete Summary of Academician Dong Chen's Research Results

Abstract 1.
Foreword: Introduction by Academician Dong Chen 2.
Research direction 1: Th17 cells 3.
Research direction 2: Tfh cells 4.
Research direction 3: Functional application of Th cells 5.
Summary of research papers 1.
Foreword Immugent some time ago The scientific research achievements of Mr.
Zhang Zemin are summarized.
Since the corresponding tweets are very popular, the editor will continue to summarize the research results of domestic scientific research leaders
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Because the editor himself studied immunization, I wrote about Mr.
Zhang Zemin because he mainly did tumor immunity.
I believe that the friends who have read the tweet admire Mr.
Zhang Zemin's ability to do scientific research
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But the immunization master introduced by the editor today is much more influential than Mr.
Zhang Zemin.
He is Academician Dong Chen of Tsinghua University
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After searching on Google Scholar, the editor found that Mr.
Dong Chen's h-index has reached 104, and the number of citations has reached an astonishing 52,674.
You must know that Mr.
Zhang Zemin's h-index is only 57 points
.

One of the founders of modern immunology, the discoverer of B cells, Max D.
Cooper's h index is only 132
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There are many founders of modern immunology.
Why do you say this Max D.
Cooper? It is because the mentor of Academician Dong Chen is this Max D.
Cooper.
Next, the editor looked at Mr.
Dong Chen's single citations, and there were 10 papers with 1000+ papers
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You must know that for ordinary workers, there is a 1000+ paper that is a big guy in the circle, which also indirectly shows the important position of immunology in the medical field (a bit of professional boasting)
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Considering that there are too many scientific research achievements of Mr.
Dong Chen, even the 10+ articles in the newsletter at the end have hundreds of articles.
In this tweet, the editor will only briefly sort out the scientific research achievements of Academician Dong Chen.
Small partners who are interested in a certain research can download the corresponding original text for study
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The editor will classify Mr.
Dong Chen's numerous research results according to his own understanding of immunology, and summarize them from three research directions, which also correspond to several major research directions of Mr.
Dong Chen.
Let's start to interpret! 2.
Research direction 1: Th17 cells are an important T cell subtype in the human body.
Th17 cells are related to various autoimmune diseases in the human body.
Academician Dong Chen is a researcher in the field of Th17 cell (helper T cell) differentiation, regulation and function research.
One of the founders and research authorities
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Th17 cells mainly secrete interleukin 17 (IL-17).
Th17 has been found to play an important role in the occurrence of autoimmune and inflammatory diseases.
Dong Chen's laboratory discovered and identified the characteristics of Th17 cells and their role in various diseases.
The pathogenic role in the Th17 domain promotes the rapid development of Th17
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Academician Dong Chen published a research paper titled: A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17 in Nature Immunology in 2005, and together with Professor Casey Weaver discovered a new type of helper T cells - Th17 cells , this discovery broke the understanding of immunologists for more than 20 years that there are only two types of helper T cells, Th1 and Th2
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Yes, this is also the most cited study by Mr.
Dong Chen above
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It is generally believed that Th1 cells are closely related to autoimmune diseases.
Until 2003, it was found that Icos and Il23 deficiency can significantly alleviate the autoimmune response in mice, and this process is closely related to the reduction of IL-17 secretion, but is independent of Th1 cells.

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The group of IL-17-secreting cells discovered by Dong Chen is a third type of cell lineage developed from naive T cells and independent of Th1 and Th2 cells
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Casey T Weaver's group found that inhibition of Th1 and Th2 cells in vitro can enhance the development of Th17 cells, and IL-23 can further promote this process
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In addition, Dong Chen's group also found that autoimmune diseases still exist in Th1 and Th2 deficient mice
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Meanwhile, IL-17 can induce fibroblasts to secrete chemokines and metalloproteinases in vitro, and in vivo, overexpression of IL-17 can induce tissue inflammation, while blocking IL-17 inhibits multiple sclerosis in mice The infiltration of immune cells into the central nervous system in the model functionally establishes a strong link between this new class of cells and tissue inflammation
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Then Dong Chen's team discovered the important transcription factors RORA and ROEC that regulate Th17, and the corresponding results were published in the journal immunity in 2008 with an article entitled: T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma , this research is also the second most cited research by Mr.
Dong Chen
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The two studies identified a third class of CD4+ helper T cells, Th17 cells, which regulate tissue inflammation in infection and chronic inflammatory responses by secreting IL-17
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Targeting Th17 cell-related molecules has been successful in multiple clinical trials, including the treatment of psoriasis and ankylosing spondyloarthritis
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Then, in 2010, Dong Chen's team published a research report entitled: Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease in the journal immunity , which is also one of the earliest studies to reveal the pathogenic mechanism of T and 7 in autoimmune diseases
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In this study, the authors found that TLR2 expressed on T cells directly regulates Th17 cell function
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In vitro experiments showed that stimulation with TLR2 agonists also promoted Th17 differentiation and resulted in a stronger proliferative potential and cytokine production of Th17 cells
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Using an experimental autoimmune encephalomyelitis (EAE) model
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The authors also found that TLR2 regulates Th17 cell-mediated autoimmune disease in vivo, and that deletion of TLR2 in CD4+ T cells significantly ameliorated EAE
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Thus, this study uncovers a critical role for TLRs in the direct regulation of adaptive immune responses and autoimmune disease pathogenesis
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It stands to reason that the discovery of this T-cell subtype is enough to study for a lifetime, and it is enough to show off for a lifetime
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But the reason why the big guys are called big guys is that they always insist on a heart that keeps exploring the unknown
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Considering the space limitation, the article on Mr.
Dong Chen's research on Th17 cells will be introduced here first, and then the other research directions of Mr.
Dong Chen will be introduced
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3.
Research direction 2: Tfh cells In the above editor, I introduced one of the main research directions of Academician Dong Chen: the function research of Th17 cells.
The following will introduce another important discovery of him, Tfh cells
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In the third year of Mr.
Dong Chen's discovery of Th17 cells, he led his team to discover another important Tfh cell in immune cells, and the corresponding research results were also published in the journal immunity in 2008.
: Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages, this research result is also one of 10 1000+ cited papers by Dong Chen
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In this study, Dong Chen's team revealed for the first time Tfh cells that are different from the classic Th1, Th2, and Th17 cell differentiation trajectories, and also formally linked the body's two major immune systems: humoral immunity and cellular immunity
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In this study, the authors found that Tfh cells have distinct gene expression profiles and develop in vivo independently of Th1 or Th2 cell lineages
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The generation of Tfh cells is regulated by ICOS ligand (ICOSL) expressed on B cells and is dependent on interleukin-21 (IL-21), IL-6 and signal transducer and activator of transcription 3 (STAT3)
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However, unlike Th17 cells, differentiation of Tfh cells in vivo does not require transforming growth factor b (TGF-b) or the orphan nuclear receptor transcription factors (RORa and RORg) required for Th17 development
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Finally, in the presence of IL-21 but not TGF-b signaling, naive T cells activated in vitro preferentially gain Tfh gene expression and promote germinal center responses
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Therefore, this study demonstrates that Tfh is a unique Th cell line
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Then, in the second year, in 2009, Mr.
Dong Chen published another major research result of Tfh in Science in the form of Bcl6 mediates the development of T follicular helper cells.
One of Mr.
Dong Chen's 10 papers with 1000+ citations
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These two research results laid the foundation for the research of Tfh cells.
The important function of BCL6 in regulating the development of Tfh cells, which was jointly identified with other research groups, was also listed as one of the 20 landmark advances in immunology, and Introduced in Revealing T follicular helper cells with BCL6
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In addition to discovering that Bcl6 is an important regulator of Tfh differentiation and development, Mr.
Dong Chen also discovered another important regulator of Tfh in 2019: Tox2.
The corresponding results were also published in the journal Immnity, titled: The Transcription Factor Tox2 Drives T Follicular Helper Cell Development via Regulating Chromatin Accessibility
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Tfh cells provide essential help for B cells in the germinal center (GC) response, and Bcl6 is an essential transcription factor that regulates Tfh cell development
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In this study the authors investigate the molecular pathways that induce Bcl6 gene expression and highlight a Bcl6-dependent function in Tfh cell commitment
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Genome-wide analysis of integrated Bcl6 occupancy and differential gene expression in Tfh cells revealed that the transcription factor Tox2 plays an important role in Tfh cell differentiation
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Ectopic expression of Tox2 is sufficient to drive Bcl6 expression and Tfh development
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In genome-wide ChIP-seq analysis, tox2 binding sites associated with Tfh cell differentiation and function, including Bcl6; meanwhile, ATAC-seq detected Tox2 binding associated with increased chromatin accessibility at these sites
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Tox2-deficient mice exhibit Tfh differentiation defects, and inhibition of Tox2 and the related transcription factor Tox disrupts Tfh differentiation
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Thus, in this study the authors identified a Tox2-Bcl6 axis that establishes a transcriptional feedforward loop, a program that promotes Tfh differentiation
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As an important bridge cell connecting the two major immune systems of the human body: Tfh has been one of several hot research fields in the field of immunology since it was proposed.
As an authority on Tfh cell research, Academician Dong Chen also published in the journal Immunity last year.
The title is: Research paper on Costimulation molecules differentially regulating the ERK-Zfp831 axis to shape T follicular helper cell differentiation
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The discovery of Th17 and Tfh cells has greatly promoted immunologists' understanding of immune diseases, especially autoimmune diseases.
These two major discoveries have also advanced the development of new immune drugs, especially for human autoimmune diseases.
drug
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Mr.
Dong Chen has also become one of the authoritative experts in international immunology research basically relying on the research results of Th17 and Tfh, and also established his position in the field of immunology by these two major research findings
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4.
Research direction 3: The function of Th cells is applied in the above two parts.
The editor introduced the two major research areas of Mr.
Dong Chen respectively.
In addition to the research on large Th cells, research results in other fields of immunology, especially the functional research of various Th cells in actual disease models
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We know that cytokines are an important component of human immune cells, and various immune cells largely rely on the complex cytokine network to play their corresponding functions
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Dong Chen was the first to discover the important role of IL-21 in the immune system in the research on cytokines.
The corresponding research results were titled: Essential autocrine regulation by IL-21 in the generation of inflammatory T cells in 2007.
Published in Nature
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When activated, Th cells differentiate into different effector subpopulations, which are characterized by their characteristic cytokine expression and immunomodulatory functions
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During differentiation, Th1 and Th2 cells produce interferon-c and interleukin (IL)-4, respectively, as autocrine factors necessary for selective lineage commitment
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A distinct Th subset is called Th17 or inflammatory Th cells
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Differentiation of Th17 cells is initiated by transforming growth factor-b and IL-6 and enhanced by IL-23, where the signal transducer and activator of transcription STAT3 and the retinoic acid receptor-related orphan receptor ROR-c mediate lineage differentiation
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Th17 cells can produce IL-17, IL-17F and IL-22.
IL-17, IL-17F and IL-22 can all regulate inflammatory responses through tissue cells, but are not important for Th17 differentiation
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We found that IL-21 is another cytokine highly expressed by mouse Th17 cells
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IL-21 is induced by IL-6 in activated T cells, and this process is dependent on STAT3 rather than ROR-c
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IL-21 induces TH17 differentiation and inhibits the expression of Foxp3, which requires STAT3 and Rorc-encoded ROR-c
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IL-21 deficiency impairs TH17 cell production and results in protection against experimental autoimmune encephalomyelitis
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Therefore, IL-21 is an autocrine cytokine necessary for TH17 differentiation and a target for the treatment of inflammatory diseases
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Another important cytokine regulation mechanism discovered by Dong Chen is IL-9.
The corresponding research results were published in the journal Nature Immunology in 2010 under the title: Regulation of IL-9 expression by IL-25 signaling
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The physiological regulation of the expression of interleukin 9 (IL-9), a cytokine traditionally associated with Th2 cells, is unclear
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In this study, the authors found that IL-9-expressing T cells were generated in vitro in the presence of transforming growth factor-B and IL-4, mRNA for IL-17 receptor B (the receptor for IL-25) high level
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However, after treatment of these cells with IL-25, the expression of IL-9 could be enhanced in vitro
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Furthermore, transgenic and retroviral overexpression of IL-17RB in T cells resulted in IL-25-induced IL-9 production, whereas IL-4 was independent
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In vivo, IL-25 and IL-17rb pathways regulate IL-9 expression in allergic airway inflammation
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Therefore, IL-25 is a newly discovered important factor that can regulate the expression of IL-9
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In addition to his research on autoimmune diseases, Mr.
Dong Chen also has many achievements in tumor research, one of which is the title of Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid published in the journal Immunity in 2018 Cells Induces Dysfunction of Anti-tumor CD8 + T Cells
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We know that programmed death ligand-1 (PD-L1) is upregulated on tumor cells, and that PD-1/PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting the presence of T Other mechanisms of cellular exhaustion
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B7 superfamily member 1 (B7S1), also known as B7-h4, B7x, or VTCN1, negatively regulates T cell activation
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In this study, the authors found that increased B7S1 expression in human hepatocellular carcinoma myeloid cells is associated with CD8+ T cell dysfunction
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B7S1 inhibits tumor development in mice
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It is speculated that the B7S1 receptor is co-expressed with PD-1, but not T-cell immunoglobulin and mucin domain 3 (Tim-3), in the activated state of early tumor-infiltrating CD8+ T cells, so B7S1 may promote T through Eomes overexpression Cell failure
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The authors also found that when B7S1 and PD-1 were blocked at the same time, there was a synergistic enhancement of antitumor immune responses
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Collectively, B7S1 triggers tumor-infiltrating CD8+ T cell dysfunction and may be a target for cancer immunotherapy
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In recent years, all walks of life around the world have been affected by the new crown virus.
As one of the hot research fields of immunology in recent years, the new crown is a research direction that many major immunologists will participate in.
Mr.
Dong Chen also has a major role in the new crown research.
It was found that the corresponding results were published in the journal Immunity in 2020 under the title: Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8 + T Cells
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The study collected blood from newly discharged patients with COVID-19 and detected SARS-cov-2-specific humoral and cellular immunity in eight newly discharged patients
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A follow-up analysis of another group of 6 patients 2 weeks after discharge also found higher immunoglobulin G (IgG) antibody titers
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Of all 14 patients tested, 13 patients who entered the trial as pseudotypes showed serum neutralizing activity
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Notably, there was a strong correlation between neutralizing antibody titers and the number of virus-specific T cells
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The work of this study provides a basis for further analysis of the protective immunity of SARS-CoV-2 to understand the pathogenesis of COVID-19, especially in severe cases
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In addition, this study has great implications for the efficient development of vaccines against SARS-CoV-2 infection
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5.
It is said that in the end, there are two top journals in the field of immunology, one is the journal of immunity under Cell, and the other is journal of Nature immunology under Nature.
Those who can publish a research paper in these two journals are even in immunity.
He has made great achievements in the circle, and if he publishes two articles locally, he has the strength to run for outstanding youth
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And every research paper of Academician Dong Chen we introduced above has been published in at least these two journals, which shows its important position in the field of immunology
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In fact, some of the articles introduced above are actually representative works of Academician Dong Chen in several directions.
In addition, he also has many other research papers.
Due to space limitations, the editor will not introduce them one by one here
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However, in order to facilitate everyone to systematically study the research results of Mr.
Dong Chen, the editor lists all the high-scoring articles of Mr.
Dong Chen up to now with the last communication, and they have been sorted in positive order.
You can Choose the articles you are interested in to study
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2020 Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals.
2020 Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells2021 Costimulation molecules differentially regulate the ERK-Zfp831 axis to shape T follicular helper cell differentiation.
2021 Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.
For more information on bioinformatics analysis: 18501230653 (same number on WeChat) Bioinformatics analysis good text recommendation 01 A full summary of Zhang Zemin's series of research results 02 Proteomics: The accessible cancer targets actually come from the peritumoral microenvironment 03 Space metabolism + drug resistance can still do this! 04Tobacco and cancer05Immune-related adverse effects: an overview 2020 Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells2021 Costimulation molecules differentially regulate the ERK-Zfp831 axis to shape T follicular helper cell differentiation.
2021 Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.
More Letter analysis question consultation: 18501230653 (same number on WeChat) Health letter analysis good article recommendation 01 A full summary of Zhang Zemin's series of research results 02 Proteomics: Cancer targets within reach actually come from the peritumoral microenvironment 03 Spatial metabolism + drug resistance is unexpectedly still It can be done! 04Tobacco and cancer05Immune-related adverse effects: an overview 2020 Febrile Temperature Critically Controls the Differentiation and Pathogenicity of T Helper 17 Cells2021 Costimulation molecules differentially regulate the ERK-Zfp831 axis to shape T follicular helper cell differentiation.
2021 Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.
More Letter analysis question consultation: 18501230653 (same number on WeChat) Health letter analysis good article recommendation 01 A full summary of Zhang Zemin's series of research results 02 Proteomics: Cancer targets within reach actually come from the peritumoral microenvironment 03 Spatial metabolism + drug resistance is unexpectedly still It can be done! 04Tobacco and cancer05Immune-related adverse effects: an overview