CN114748623A - Method for enhancing Treg cell function in vivo - Google Patents
Method for enhancing Treg cell function in vivo Download PDFInfo
- Publication number
- CN114748623A CN114748623A CN202210384399.2A CN202210384399A CN114748623A CN 114748623 A CN114748623 A CN 114748623A CN 202210384399 A CN202210384399 A CN 202210384399A CN 114748623 A CN114748623 A CN 114748623A
- Authority
- CN
- China
- Prior art keywords
- foxp3
- cells
- treg cells
- expression
- treg
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0634—Cells from the blood or the immune system
- C12N5/0636—T lymphocytes
- C12N5/0637—Immunosuppressive T lymphocytes, e.g. regulatory T cells or Treg
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2501/00—Active agents used in cell culture processes, e.g. differentation
- C12N2501/60—Transcription factors
Abstract
The invention belongs to the technical field of immunity, and particularly relates to a product and a method for enhancing the function of Treg cells in vivo. The invention firstly provides a product for enhancing the function of the Treg cells in vivo, and the product can be used for intervening the expression of the FOXP3 delta 2 protein of the Treg cells and inhibiting the expression of the FOXP3 protein. Researches find that the expression of FOXP3 delta 2 can not only enhance the binding capacity of FOXP3 to DNA and be more beneficial to the stability of Treg cells, but also ensure that the transcription spectrum of FOXP3 delta 2Treg cells in intestinal tracts is more like ROR gamma t+Treg cells enhance the function of the Treg cells and have the potential of being applied to patients with IBD in clinic.
Description
Technical Field
The invention relates to the technical field of immunization, and in particular relates to a method for enhancing the function of Treg cells in vivo.
Background
Regulatory T cells (tregs) exert an immune negative regulatory function in the body, and their relationship with effector T cells, like the wings of birds and the wheels of cars, is lacking, and only if they are in balance, can the human body be maintained in a healthy state.
Inflammatory bowel disease (inflam)IBD) is a group of chronic, recurrent, inflammatory Bowel diseases. The pathogenesis of IBD is not completely understood, and a large number of studies have shown that the interaction between intestinal microorganisms, intestinal epithelial cells and immune cells is widely involved in the pathogenesis of IBD. ROR gamma t +Treg cells are a population of pTreg (epithelial derived Tregs) cells enriched in the gut and can exert suppressive function by secreting the suppressive cytokine IL-10, and IL10 knockout mice suffer from spontaneous enteritis at 2-4 months. And in the intestinal tract of GF mice and antibiotic-treated mice, ROR γ t+Treg cells and IL-10+The number of Treg cells is reduced. In Treg cells, the specific knockout of ROR γ t expression also makes mice more susceptible to colitis.
Research shows that the balance of tregs and Th17 is an important factor for maintaining immune homeostasis of the body, and the imbalance of differentiation of tregs and Th17 plays an important role in the occurrence and development of inflammatory bowel diseases. The clinical pathological manifestations of colitis can be improved by transferring Treg cells into a mouse body, colitis of SCID mice can be improved by adoptive transfer of Treg cells expanded by rapamycin, but in clinical application, FOXP3 is lost and proinflammatory cytokines are expressed after the Treg cells are adoptively transferred into the body, and the fact that pTreg cells play a restraining function in enteritis mainly has a profound significance on how to better induce functional and stable pTreg cells in the body.
Unlike mouse Treg cells, human Treg cells can simultaneously express two forms of proteins, namely FOXP3 and splice FOXP3 delta 2 (second exon deletion), and the two forms of proteins respectively play specific functions, and whether the ratio of the two forms of proteins is related to chronic diseases and autoimmune diseases or not is not clearly concluded at present.
There are studies in which IL17 was detected in IBD patients+FOXP3+The Treg cells of (a) accumulate at the inflammatory site and the population of cells still has suppressive activity in vitro. Since FOXP3 antagonizes regulation of IL-17 by ROR γ t via the second exon, whether IBD patients prefer to express FOXP3 Δ 2 protein in Treg cells is nowThere has been no clear conclusion.
Disclosure of Invention
In response to the deficiencies of the prior art, the present invention provides a method of enhancing Treg cell function in vivo.
The invention firstly provides a product for enhancing the function of Treg cells in vivo, and the product can intervene in the expression of the FOXP3 delta 2 protein of the Treg cells and inhibit the expression of the FOXP3 protein.
Preferably, the Treg cells are CD4+T cells.
The function of the Treg cells is intervened by regulating the expression form of the Treg cell surface protein, so the invention also provides the application of the product in preparing the medicament for intervening the function of the Treg cells.
The invention also provides the application of the product in preparing a medicament for clinically treating IBD.
Another object of the present invention is to provide a method for modulating the expression level of helper T cell proteins, inhibiting CD4, for non-therapeutic purposes+The FOXP3 protein is expressed in T cells.
The invention also provides the use of the above method for non-therapeutic purposes in enhancing Treg cell function in vivo.
Compared with the prior art, the invention has the beneficial effects that:
the invention researches a method for enhancing the function of Treg cells in vivo, different from mouse Treg cells, human Treg cells can simultaneously express proteins in two forms of FOXP3 and shear body FOXP3 delta 2 (the second exon is deleted), the invention only expresses FOXP3 delta 2 by regulating and controlling the Treg cells, and the result shows that the invention can enhance the binding capacity of FOXP3 to DNA, higher expresses Thy1.1 molecules in the Treg cells expressing FOXP3 delta 2, ensures that the Treg cells are more stable, and the transcription spectrum of the group of cells in intestinal tracts is more like ROR gamma t+Treg cells have stronger inhibition function, inhibit the differentiation of Th17 cells, and have the potential of being applied to patients with IBD clinically.
Drawings
FIG. 1 is a graph showing the effect of FOXP3 Δ 2 on the binding ability of FOXP3 to DNA: (A) functional domain of FOXP3, represented by different colors: n181 (cyan), exon 2 (blue), zinc finger (yellow), leucine zipper (magenta), FKH (red), others (green); (B) the ratio of firefly luciferase to sea cucumber luciferase; experimental results were from more than three independent replicates, statistical using t-test, "ns" for no statistical difference, × for P <0.05, difference was significant; represents P <0.01, the difference is very significant; p <0.001, the difference was very significant.
Figure 2 is the effect of FOXP3 Δ 2 on Treg cell stability: (A) the expression detection of FOXP3 in example 3; (B) counting the proportion of WT Treg cells and FOXP3 delta 2Treg cells in the iTreg cells generated in vitro and the expression intensity of FOXP 3; (C-D) expression analysis of Thy1.1 in two populations of Treg cells; (E) thy1.1 in two populations of Treg cells+And (5) counting the proportion of the cells. The experimental results are from more than three independent replicates, and the statistics are determined by using t-test, "ns" for no statistical difference, and "P" for P<0.05, significant difference; represents P<0.01, the difference is very significant; represents P<0.001, the difference is very significant.
Fig. 3 is an analysis of the inhibitory function of FOXP3 Δ 2Treg cells in the intestinal tract: (A) the volcano chart shows ROR gamma t in WT Treg cells or FOXP3 delta 2Treg cells+Treg cell specific transcript profiles, red-colored in ROR γ t+Genes up-regulated in Treg cells, blue labeled down-regulated; (B-C) is the expression (B) and the statistical result (C) of ROR gamma t, C-Maf, Gata3, ST2, IL-17A and GPR15 in total Treg cells in the intestinal lamina propria by flow analysis, wherein the cells which can be marked by FOXP3(FJK-16s) are WT Treg cells, and the cells which cannot be marked by FOXP3 delta 2Treg cells; (D) for flow analysis of the intestinal lamina propria, the proportion of IL-17A secreted by Tcvon cells and statistics were performed. The experimental results are from more than three independent replicates, and the statistics are determined by using t-test, "ns" for no statistical difference, and "P" for P <0.05, the difference is significant; represents P<0.01, the difference is very significant; represents P<0.001, the difference is very significant.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The test methods used in the examples of the present invention are all conventional methods unless otherwise specified; the materials, reagents and the like used are, unless otherwise specified, commercially available reagents and materials.
EXAMPLE 1 transfection of 293T cells
(1) The sub-cultured 293T cells were plated in 24-well plates at 2X 105Each well of each cell, DMEM medium volume 500. mu.L, in 5% CO2The culture was carried out in an incubator at 37 ℃ for 12 hours.
(2) After the cells were attached, transfection was performed with Lipofectamine2000 transfection reagent. mu.L of transfection reagent per well was mixed with 25. mu.L of opti-MEM, carefully mixed and incubated for 5min at room temperature (at least two duplicate wells per set).
(3) According to the concentration of the extracted plasmids, sucking a certain volume of mutant plasmids or control plasmids such as pGL3-NB 14350 ng, internal reference plasmids 5ng, FOXP3 and the like 350ng, respectively adding the mutant plasmids or the control plasmids into 25 mu L of opti-MEM, uniformly mixing, and incubating for 5min at room temperature.
(4) mu.L of the opti-MEM containing the transfection plasmid and 25. mu.L of the opti-MEM containing Lipofectamine 2000 were gently mixed and incubated at room temperature for 5 min.
(5) The above reagents were added to 293T cells. And gently shaking the 24-well plate to allow the transfection reagent to contact the cells sufficiently and uniformly. Then, the 24 wells were cultured in a 5% CO2 incubator at 37 ℃ for 24-48 h.
Example 2 cell lysis and fluorescence assay
(1) Transfected cells were washed once with 1 × PBS and the supernatant discarded.
(2) Add 50. mu.L of 1 Xpassive lysis buffer and shake the mixture at room temperature for 15 min.
(3) After the cells were lysed completely, the lysate was placed on ice (to prevent errors in different wells due to continued lysis of the cells during the fluorometric assay).
(4) Detection of dual fluorescence was performed with a Promega fluorometer: adding 20 mu L LARII substrate into 4 mu L cell lysate, and measuring fluorescence signal of firefly; continuously adding 20 mu L of Stop reagent, and measuring the fluorescence signal of the internal sea cucumber.
(5) The instrument reads the two fluorescence signals, calculates the ratio of the two fluorescence signals and derives data.
Example 3 Induction of iTreg cells
From FOXP3WT/Δ2Enrichment of peripheral lymph nodes in mice with magnetic beads for CD4+T cells were cultured in 24-well plates previously coated with anti-CD3anti-CD28 antibody in 1640RPMI medium containing IL-2, TGF-. beta.and RA for five days, and then expression of FOXP3 was detected.
Example 4 acquisition of mouse colon lamina propria lymphocytes
(1) Dissecting and separating intestinal tract
1) Quickly killing mice by cervical dislocation, then spraying 75% alcohol on body surface for disinfection, cutting off abdominal skin and peritoneum, taking out large intestine, and placing in DMEM medium containing 2% FBS;
2) carefully remove the adherent fat on the intestine and cut away the Peyer's Patch with a pair of scissors;
3) the intestine was cut open longitudinally and rinsed clean with 1 × PBS.
(2) Predigesting and removing epithelial cells from intestinal tract
1) Cutting the section of intestine to 1-2cm and transferring to a pre-heated 50mL tube containing 25mL Predigest solution I at 37 ℃;
2) mixing at 37 deg.C in thermostat at 50rpm for 20 min;
3) swirling for 7s, pouring the liquid containing the intestinal segment into a plate;
4) repeating the steps 1-3;
5) transfer the intestinal section sample to a 37 ℃ pre-heated 50mL tube containing 25mL Predigest solution II;
6) mixing at 37 deg.C in thermostat at 50rpm for 20 min;
7) vortex for 7s and pour the liquid containing the bowel segment into a dish.
(3) Digesting and obtaining intestinal lamina propria cells
1) Washing the predigested intestinal segment with 1 × PBS for 2-3 times, and removing residual EDTA and DTT;
2) cutting the sausage section to 1-2mm by using a pair of scissors;
3) each intestinal sample was transferred to a 15mL tube containing 5mL Digest solution pre-warmed at 37 ℃;
4) mixing at 37 deg.C constant temperature for 20min at 35 rpm;
5) centrifuging at 300rpm and 4 ℃ for 4 min;
6) the supernatant was transferred to a new 15mL tube, 5mL PBS was added, centrifuged at 2000rpm for 3min, resuspended in DMEM containing 2% FBS, and placed on ice;
7) an additional 5mL of 37 ℃ preheat Digest solution was added to the undigested section of intestine;
8) mixing in 37 deg.C thermostat at 35rpm for 20min until the intestinal segments are completely digested;
9) centrifuging at 2000rpm and 4 ℃ for 3 min;
10) resuspend the pellet with 1 × PBS and add the cells from step 6;
11) centrifuging at 2000rpm and 4 ℃ for 3 min;
12) the precipitate is intestinal lamina propria cells.
(4) Percoll gradient centrifugation to obtain intestinal lamina propria lymphocytes
1) Resuspending intestinal lamina propria cells with 5mL of 40% Percoll solution;
2) carefully add 2.5mL of 80% Percoll solution from the bottom of the tube with a 3mL pipette;
3)1000g, 25 ℃ deceleration centrifugation for 20 min;
4) carefully pipette lymphocytes located at the junction of 40% and 80% Percoll solutions into 15mL tubes with a pipette gun, adding 1 × PBS to 12 mL;
5) Centrifuging at 2000rpm and 4 ℃ for 3 min;
6) the precipitate is intestinal lamina propria lymphocytes.
Experimental example 1 Effect of FOXP3 Δ 2 on the binding ability of FOXP3 to DNA
The FOXP3 protein, including a proline-rich N-terminus, a Zinc finger protein domain (ZF), a Leucine zipper domain (LZ) and a Forkhead domain (Forkhead domain, FKH) at the C-terminus, is shown in fig. 1A. Among them, the FKH domain at the C-terminus can bind to GTAAACA pattern sequences, the LZ domain has an important role in forming homo-or heterodimers with FOXP3, mutations in the LZ domain, whether naturally occurring in IPEX patients or induced by targeted mutations, significantly affect the FOXP3 function by inhibiting homo-dimerization of FOXP3, while 181 amino acids at the C-terminus inhibit its ability to bind to DNA. Another alternative variant FOXP3 FOXP3 Δ 2 deleted the second Exon just at the N-terminus (Exon2), we found that Exon2 was crucial for binding FOXP3 to DNA, and we verified that FOXP3 Δ 2 could significantly enhance its binding ability to DNA by an in vitro dual fluorescence reporter system (see fig. 1B), while deletion of the first and third exons also at the N-terminus did not significantly enhance its binding ability.
Experimental example 2 Effect of FOXP 3. DELTA.2 on Treg cell stability
The antibody with the clone number of FJK-16s recognizes the first exon of FOXP3, so that cells expressing FOXP3 and FOXP3 delta 2 can be simultaneously marked with fluorescent groups, and the other antibody with the clone number of NRRF-30 or MF23 recognizes the second exon of FOXP3, and only Treg cells expressing FOXP3 can be marked with fluorescent groups, so that the Treg cells expressing FOXP3 and FOXP3 delta 2 can be accurately distinguished. The results of the expression test of FOXP3 in example 3 are shown in fig. 2A. Statistics of the ratio of WT Treg cells to FOXP3 Δ 2Treg cells and the expression intensity of FOXP3 in vitro generated iTreg cells are shown in fig. 2B. The results show that compared with FOXP3, FOXP Δ 2 expression does not affect the induction of Treg cells in vitro, but rather the expression intensity of FOXP3 is higher in the generated Treg cells.
A FOXP3-exon2 KO mouse is constructed by the gene editing technology of Crispr/Cas9, and the mouse survives normally and does not have lethal autoimmune disease. And simultaneously using FOXP3 preserved in a laboratory with usΔCNS1- Thy1.1Rosa26YFP tracer mice were mated because we found in previous studies that Treg cells lost expression of thy1.1 first and then FOXP3, and that thy1.1 expression was indicative of Treg cell stability, and thy1.1 in both populations of Treg cells Expression analysis, Thy1.1 in two Treg populations+The cell ratios were statistically shown in FIGS. 2C-2E. The results show that the thy1.1 molecule is more highly expressed in Treg cells expressing FOXP3 delta 2, and the Treg cells are more stable.
Experimental example 3 inhibition function of FOXP3 delta 2Treg cells in intestinal tract
By transcriptome sequencing, we found that in the lamina propria of the intestinal tract, transcription factors ROR γ t and ROR γ t are up-regulated in Treg cells if FOXP3 Δ 2 is expressed+Expression of Treg cell-associated genes with a transcriptional profile more like ROR gamma t+Treg cells (see fig. 3A). The population of cells highly expressed C-Maf, IL-17A, did not express ST2, Gata3 and Helios, and low expressed the homing molecule GPR15 (see FIGS. 3B-C). The presence of this population of cells had a stronger inhibitory effect than that of WT mice, inhibiting the differentiation of Th17 cells (see fig. 3D).
The above-mentioned embodiments of the present invention are merely examples for clearly illustrating the technical solutions of the present invention, and are not intended to limit the specific embodiments of the present invention. Any modification, equivalent replacement, and improvement made within the spirit and principle of the present invention claims should be included in the protection scope of the present invention claims.
Claims (6)
1. A product for enhancing the function of Treg cells in vivo, wherein the product is capable of interfering with the expression of FOXP3 delta 2 protein by Treg cells and inhibiting the expression of FOXP3 protein.
2. The product for enhancing the function of Treg cells in vivo as claimed in claim 1 wherein said Treg cells are CD4+T cells.
3. Use of a product according to any of claims 1 or 2 in the manufacture of a medicament for interfering with the function of Treg cells.
4. Use of a product according to any one of claims 1 or 2 in the manufacture of a medicament for the clinical treatment of inflammatory bowel disease.
5. A method for regulating and controlling the expression level of helper T cell protein in a non-treatment purpose is characterized in that the expression of FOXP3 delta 2 protein in Treg cells is interfered, and meanwhile, the expression of FOXP3 protein in the Treg cells is inhibited.
6. Use of the method of claim 5 for enhancing Treg cell function in vivo for non-therapeutic purposes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210384399.2A CN114748623A (en) | 2022-04-13 | 2022-04-13 | Method for enhancing Treg cell function in vivo |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210384399.2A CN114748623A (en) | 2022-04-13 | 2022-04-13 | Method for enhancing Treg cell function in vivo |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114748623A true CN114748623A (en) | 2022-07-15 |
Family
ID=82330196
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210384399.2A Pending CN114748623A (en) | 2022-04-13 | 2022-04-13 | Method for enhancing Treg cell function in vivo |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114748623A (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013151490A1 (en) * | 2012-04-02 | 2013-10-10 | John Andersson | Methods and compounds for treating diseases |
| CN110139675A (en) * | 2016-10-31 | 2019-08-16 | 西雅图儿童医院（Dba西雅图儿童研究所） | With the method with the CD4 T cell for being engineered stable endogenous FOXP3 gene expression treatment autoimmune disease |
-
2022
- 2022-04-13 CN CN202210384399.2A patent/CN114748623A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013151490A1 (en) * | 2012-04-02 | 2013-10-10 | John Andersson | Methods and compounds for treating diseases |
| CN110139675A (en) * | 2016-10-31 | 2019-08-16 | 西雅图儿童医院（Dba西雅图儿童研究所） | With the method with the CD4 T cell for being engineered stable endogenous FOXP3 gene expression treatment autoimmune disease |
Non-Patent Citations (3)
| Title |
|---|
| MAILER REINER K.: "IPEX as a Consequence of Alternatively Spliced FOXP3", 《FRONTIERS IN PEDIATRICS》 * |
| T. AARTS-RIEMENS ET AL.: "Forced overexpression of either of the two common human Foxp3 isoforms can induce regulatory T cells from CD4CD25+– cells", 《EUR. J. IMMUNOL.》 * |
| YOHEI SATO ET AL.: "Co-Expression of FOXP3FL and FOXP3Delta2 Isoforms Is Required for Optimal Treg-Like Cell Phenotypes and Suppressive Function", 《FRONT. IMMUNOL.》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Najafova et al. | BRD4 localization to lineage-specific enhancers is associated with a distinct transcription factor repertoire | |
| Fang et al. | Transient T-bet expression functionally specifies a distinct T follicular helper subset | |
| Tata et al. | Developmental history provides a roadmap for the emergence of tumor plasticity | |
| Zwarycz et al. | IL22 inhibits epithelial stem cell expansion in an ileal organoid model | |
| Zhou et al. | PBX1 expression in uterine natural killer cells drives fetal growth | |
| Roychoudhuri et al. | BACH2 represses effector programs to stabilize Treg-mediated immune homeostasis | |
| Mourikis et al. | Cell-autonomous Notch activity maintains the temporal specification potential of skeletal muscle stem cells | |
| Siddiqui et al. | Epithelial miR-141 regulates IL-13–induced airway mucus production | |
| Li et al. | Exosomes from LNCaP cells promote osteoblast activity through miR‑375 transfer | |
| Di Foggia et al. | Bmi1 enhances skeletal muscle regeneration through MT1-mediated oxidative stress protection in a mouse model of dystrophinopathy | |
| Preglej et al. | Histone deacetylases 1 and 2 restrain CD4+ cytotoxic T lymphocyte differentiation | |
| Tumes et al. | Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology | |
| Xu et al. | Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease | |
| Faass et al. | Contribution of Heptose Metabolites and the cag Pathogenicity Island to the Activation of Monocytes/Macrophages by Helicobacter pylori | |
| Malinverno et al. | Peg3/PW1 is a marker of a subset of vessel associated endothelial progenitors | |
| Suthapot et al. | The RNA helicases DDX5 and DDX17 facilitate neural differentiation of human pluripotent stem cells NTERA2 | |
| Enderes et al. | A population of radio-resistant macrophages in the deep myenteric plexus contributes to postoperative ileus via toll-like receptor 3 signaling | |
| Teng et al. | Tfh exosomes derived from allergic rhinitis promote DC maturation through miR-142-5p/CDK5/STAT3 pathway | |
| Gayraud-Morel et al. | Notchless defines a stage-specific requirement for ribosome biogenesis during lineage progression in adult skeletal myogenesis | |
| CN114748623A (en) | Method for enhancing Treg cell function in vivo | |
| Nemeth et al. | A novel fibroblast reporter cell line for in vitro studies of pulmonary fibrosis | |
| Stathopoulou et al. | CHARGE syndrome-associated CHD7 acts at ISL1-regulated enhancers to modulate second heart field gene expression | |
| CN105452861A (en) | In vitro method for assessing cytokine storm responses | |
| Cordeiro et al. | MicroRNA-9 fine-tunes dendritic cell function by suppressing negative regulators in a cell-type-specific manner | |
| Zur Bruegge et al. | Intestinal organoids in colitis research: focusing on variability and cryopreservation |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |