The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
TGFβ directs gene expression of activated microglia to an anti‐inflammatory phenotype strongly focusing on chemokine genes and cell migratory genes
Open accessAbstract
In experimental autoimmune encephalomyelitis, the acute phase of the disease is produced by T‐helper lymphocyte type 1 (T H 1), which produces mainly TNFα and IFNγ. Recovery from the disease is mediated by T‐helper lymphocyte types 2 and 3 (T H 2/T H 3), which, among other cytokines, produce transforming growth factor β (TGFβ). To address the influence of TGFβ on T H 1‐induced gene expression, microarray technology was used on murine primary microglial cells stimulated with IFNγ and TNFα in the absence or presence of TGFβ. The resulting data from an investigation of up to 5,500 genes provided the notion that TGFβ prevents the induction of a proinflammatory gene program within microglia exposed to a T H 1 milieu. T H 1 cytokines upregulated 175 genes comprising cytokine, chemokine, and genes involved in host response to infection and the TNFα/IFNγ intracellular signaling pathway. It is observed that TGFβ inhibits expression of 25% of the TNFα/IFNγ‐induced genes and a further 66 TNFα/IFNγ‐independent genes. The focus of TGFβ inhibition is observed to be directed in genes involved in chemotaxis (IL‐15, CXCL1, CXCL2, CCL3, CCL4, CCL5, CCL9), chemokine receptors (CCR5, CCR9), LIF receptor, and FPR2, and on genes mediating cell migration (MMP9, MMP13, MacMARCKS, endothelin receptor B, Ena/VASP, Gas7), apoptosis (FAS, TNF, TNF receptor, caspase‐1 and ‐11), and host response to infection (toll‐like receptor 6, Mx‐1, and MARCO). Taken collectively, the data strongly suggest that one of the main effects of TGFβ is to impair cell entry into the CNS and to hinder migration of microglia in the CNS parenchyma. © 2003 Wiley‐Liss, Inc.
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“All three microglial sub-populations showed upregulation of APOE, ATG16L2 (an autophagy antagonist gene), BCL2 (encoding a negative regulator of apoptosis), the CDK7 regulator gene CCNH and GAS7 (the growth arrest-specific protein 7 gene). Genes for negative regulators of senescence such as GRB2 and NIBAN1 were downregulated with increasing β-amyloid [17, 21, 34, 55].”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [55]
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“MMP9 is an important Aβ-degrading enzyme expressed on microglia (25) and neurons (26).”
From Heterozygous CX3CR1 Deficiency in Microglia Restores Neuronal β-Amyloid Clearance Pathways and Slows Progression of Alzheimer's Like-Disease in PS1-APP Mice (2019) · cites this paper as [25]
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Metadata
- Authors
- Paglinawan, R., Malipiero, U., Schlapbach, R., Frei, K., Reith, W., & Fontana, A.
- Affiliations
- University Hospital Zurich (CH)
- Functional Genomics Center Zurich (CH)
- University of Geneva (CH)
- Corresponding author
- Fontana, Adriano
- ORCID
- Schlapbach, Ralph
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2003-08
- Volume
- 44
- Issue
- 3
- Pages
- 219-231
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2022786490
- Cited by
- 122
- References
- 43
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 6 · 2018: 6 · 2017: 5 · 2016: 9 · 2015: 7 · 2014: 4 · 2013: 8 · 2012: 4
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- TGF-beta, microglia, experimental autoimmune encephalomyelitis, Th1 cytokines, interferon-gamma, TNF-α, anti-inflammatory phenotype, chemokine genes, cell migration, chemotaxis, chemokine receptors, apoptosis, host response to infection, gene expression profiling
- MeSH terms
- Animals, Cell Movement, Encephalomyelitis, Autoimmune, Experimental, Gene Expression Regulation, Phenotype, Specific Pathogen-Free Organisms, Transforming Growth Factor beta, Apoptosis, Microglia, Chemokines, Oligonucleotide Array Sequence Analysis, Mice, Transforming Growth Factor beta2
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