Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration.
Age-associated sterile inflammation can cause dysregulated choroidal neovascularization (CNV) as age-related macular degeneration (AMD). Intraocular fluid screening of 234 AMD patients identified high levels of IL-4. The purpose of this study was to determine the functional role of IL-4 in CNV formation using murine CNV model. Our results indicate that the IL-4/IL-4 receptors (IL4Rs) controlled tube formation and global proangiogenic responses of bone marrow cells. CCR2+ bone marrow cells were recruited to form very early CNV lesions. IL-4 rapidly induces CCL2, which enhances recruitment of CCR2+ bone marrow cells. This in vivo communication, like quorum-sensing, was followed by the induction of IL-4 by the bone marrow cells during the formation of mature CNVs. For CNV development, IL-4 in bone marrow cells are critically required, and IL-4 directly promotes CNV formation mainly by IL-4R. The IL-4/IL-4Rα axis contributes to pathological angiogenesis through communications with bone marrow cells leading to retinal degeneration.
Pubmed ID: 32366355 RIS Download
Research resources used in this publication
- C57BL/6-Tg(CAG-EGFP)1Osb/J (RRID:IMSR_JAX:003291) (organism)
- Il13ra1tm1Twy (RRID:MGI:3772446) (organism)
- BALB/c-Il4ratm1Sz/J (RRID:IMSR_JAX:003514) (organism)
- C57BL/6J (RRID:IMSR_JAX:000664) (organism)
- GENESPRING GT (RRID:SCR_009196) (software resource)
- C57BL/6-Il4tm1Nnt/J (RRID:IMSR_JAX:002518) (organism)
- Stata (RRID:SCR_012763) (software resource)
- Adobe Photoshop (RRID:SCR_014199) (software resource)
- Ingenuity Pathway Analysis (RRID:SCR_008653) (pathway analysis tool)
Additional research tools detected in this publication
Antibodies used in this publication
- Rat IgG2A Isotype Control (Clone 54447) (RRID:AB_357349)
- Brilliant Violet 421(TM) Goat anti-rat IgG (minimal x-reactivity) (RRID:AB_10900808)
- Alexa Fluor(R) 647 anti-mouse CD31 (RRID:AB_2161029)
- DyLight(TM) 649 Donkey anti-rabbit IgG (min. x-reactivity) (RRID:AB_1575135)
- IL4 antibody (RRID:AB_308736)
- Anti-CD31 antibody (RRID:AB_726362)
- LEAF™ Purified anti-mouse IL-4 (RRID:AB_315322)
- Donkey Anti-Rabbit IgG H&L (Alexa Fluor® 647) (RRID:AB_2752244)
- Anti Iba1, Rabbit antibody (RRID:AB_839504)
- CD11b Monoclonal Antibody (M1/70), FITC, eBioscience (RRID:AB_11042156)
- LEAF(TM) Purified anti-mouse/rat/human MCP-1 (RRID:AB_2071552)
- goat anti-rabbit IgG-PE (RRID:AB_649004)
- Alexa Fluor(R) 594 anti-mouse/human CD11b (RRID:AB_2563231)
- DyLight(TM) 594 Goat anti-hamster (Armenian) IgG (RRID:AB_1575119)
- CD11b Monoclonal Antibody (M1/70), eBioscience (RRID:AB_467108)
- IL13 receptor alpha 1 antibody (RRID:AB_1640587)
- Alexa Fluor(R) 555 Donkey anti-rabbit IgG (minimal x-reactivity) (RRID:AB_2563181)
- Rat Anti-CD124 Monoclonal Antibody, Unconjugated, Clone mIL4R-M1 (RRID:AB_394356)
- DyLight 488 Anti-Rabbit IgG (H+L), made in goat (RRID:AB_2336402)
- Rabbit Anti-IL-4R/CD124 (Phospho-Tyr497) Polyclonal, Unconjugated (RRID:AB_10683571)
- VECTASHIELD Mounting Medium (RRID:AB_2336789)
- GSL I - isolectin B4 (GSL I-B4 , BSL I-B4 ) (RRID:AB_2314663)
Associated grants
- Agency: Japan Society for the Promotion of Science, International
Id: JP16K15733 - Agency: Japan Society for the Promotion of Science, International
Id: JP25670733
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ATCC (tool)
RRID:SCR_001672
Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNovus Biologicals (tool)
RRID:SCR_004286
Commercial antibody vendor which supplies antibodies and other products to life science researchers.
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RRID:SCR_006140
An Antibody supplier who also provides assay services and products.
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RRID:SCR_008539
A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.
View all literature mentionsSigma-Aldrich (tool)
RRID:SCR_008988
American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsAbcam (tool)
RRID:SCR_012931
A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsMolecular Probes (tool)
RRID:SCR_013318
An Antibody supplier and subset of ThermoFisher Scientific which provides fluorescence reagents for various experiments and methods.
View all literature mentionsRat IgG2A Isotype Control (Clone 54447) (antibody)
RRID:AB_357349
This unknown targets Rat
View all literature mentionsBrilliant Violet 421(TM) Goat anti-rat IgG (minimal x-reactivity) (antibody)
RRID:AB_10900808
This unknown targets IgG
View all literature mentionsAlexa Fluor(R) 647 anti-mouse CD31 (antibody)
RRID:AB_2161029
This monoclonal targets CD31
View all literature mentionsDyLight(TM) 649 Donkey anti-rabbit IgG (min. x-reactivity) (antibody)
RRID:AB_1575135
This unknown targets Rabbit IgG
View all literature mentionsAnti-CD31 antibody (antibody)
RRID:AB_726362
This polyclonal targets CD31
View all literature mentionsLEAF™ Purified anti-mouse IL-4 (antibody)
RRID:AB_315322
This monoclonal targets IL-4
View all literature mentionsDonkey Anti-Rabbit IgG H&L (Alexa Fluor® 647) (antibody)
RRID:AB_2752244
This polyclonal targets IgG
View all literature mentionsAnti Iba1, Rabbit antibody (antibody)
RRID:AB_839504
This polyclonal targets Iba1
View all literature mentionsCD11b Monoclonal Antibody (M1/70), FITC, eBioscience (antibody)
RRID:AB_11042156
This monoclonal targets CD11b
View all literature mentionsLEAF(TM) Purified anti-mouse/rat/human MCP-1 (antibody)
RRID:AB_2071552
This monoclonal targets CCL2
View all literature mentionsgoat anti-rabbit IgG-PE (antibody)
RRID:AB_649004
This polyclonal targets Rabbit IgG
View all literature mentionsAlexa Fluor(R) 594 anti-mouse/human CD11b (antibody)
RRID:AB_2563231
This monoclonal targets CD11b
View all literature mentionsDyLight(TM) 594 Goat anti-hamster (Armenian) IgG (antibody)
RRID:AB_1575119
This unknown targets IgG
View all literature mentionsCD11b Monoclonal Antibody (M1/70), eBioscience (antibody)
RRID:AB_467108
This monoclonal targets CD11b
View all literature mentionsIL13 receptor alpha 1 antibody (antibody)
RRID:AB_1640587
This polyclonal targets IL13 receptor alpha 1 antibody
View all literature mentionsAlexa Fluor(R) 555 Donkey anti-rabbit IgG (minimal x-reactivity) (antibody)
RRID:AB_2563181
This unknown targets Rabbit IgG
View all literature mentionsRat Anti-CD124 Monoclonal Antibody, Unconjugated, Clone mIL4R-M1 (antibody)
RRID:AB_394356
This monoclonal targets CD124 (IL-4 Receptor)
View all literature mentionsDyLight 488 Anti-Rabbit IgG (H+L), made in goat (antibody)
RRID:AB_2336402
This unknown targets IgG
View all literature mentionsRabbit Anti-IL-4R/CD124 (Phospho-Tyr497) Polyclonal, Unconjugated (antibody)
RRID:AB_10683571
This polyclonal targets Rabbit IL-4R/CD124 (Phospho-Tyr497)
View all literature mentionsVECTASHIELD Mounting Medium (antibody)
RRID:AB_2336789
This unknown targets
View all literature mentionsGSL I - isolectin B4 (GSL I-B4 , BSL I-B4 ) (antibody)
RRID:AB_2314663
This unknown targets
View all literature mentionsC57BL/6-Tg(CAG-EGFP)1Osb/J (organism)
RRID:IMSR_JAX:003291
Mus musculus with name C57BL/6-Tg(CAG-EGFP)1Osb/J from IMSR.
View all literature mentionsIl13ra1tm1Twy (organism)
RRID:MGI:3772446
Allele Detail: Targeted This is a legacy resource.
View all literature mentionsBALB/c-Il4ratm1Sz/J (organism)
RRID:IMSR_JAX:003514
Mus musculus with name BALB/c-Il4ratm1Sz/J from IMSR.
View all literature mentionsC57BL/6J (organism)
RRID:IMSR_JAX:000664
Mus musculus with name C57BL/6J from IMSR.
View all literature mentionsGENESPRING GT (software resource)
RRID:SCR_009196
A desktop analysis workbench for analyzing high-volume, high-density genotyping data. The software provides a comprehensive set of linkage and association algorithms that allow researchers to discover relationships between genotypes and phenotypes. Researchers can visually explore fully annotated SNPs and genes at varying levels of detail. Designed for biologists and statisticians, GeneSpring GT is capable of importing, visualizing, and analyzing hundreds of thousands of variation measurements simultaneously, for rapid localization of disease or phenotype markers. (entry from Genetic Analysis Software)
View all literature mentionsC57BL/6-Il4tm1Nnt/J (organism)
RRID:IMSR_JAX:002518
Mus musculus with name C57BL/6-Il4tm1Nnt/J from IMSR.
View all literature mentionsStata (software resource)
RRID:SCR_012763
A Software resource for statistical analysis and presentation of graphics.
View all literature mentionsAdobe Photoshop (software resource)
RRID:SCR_014199
Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsIngenuity Pathway Analysis (pathway analysis tool)
RRID:SCR_008653
A web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.
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