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Ectonucleotidase activity and immunosuppression in astrocyte-CD4 T cell bidirectional signaling
- Source :
- Oncotarget
- Publication Year :
- 2019
-
Abstract
- Astrocytes play a crucial role in neuroinflammation as part of the glia limitans, which regulates infiltration of the brain parenchyma by leukocytes. The signaling pathways and molecular events, which result from the interaction of activated T cells with astrocytes are poorly defined. Here we show that astrocytes promote the expression and enzymatic activity of CD39 and CD73 ectonucleotidases in recently activated CD4 cells by a contact dependent mechanism that is independent of T cell receptor interaction with class II major histocompatibility complex (MHC). Transforming growth factor-β (TGF-β) is robustly upregulated and sufficient to promote ectonucleotidases expression. T cell adhesion to astrocyte results in differentiation to an immunosuppressive phenotype defined by expression of the transcription factor Rorγt, which characterizes the CD4 T helper 17 subset. CD39 activity in T cells in turn inhibits spontaneous calcium oscillations in astrocytes that correlated with enhanced and reduced transcription of CCL2 chemokine and Sonic hedgehog (Shh), respectively. We hypothesize this TCR-independent interaction promote an immunosuppressive program in T cells to control possible brain injury by deregulated T cell activation during neuroinflammation. On the other hand, the increased secretion of CCL2 with concomitant reduction of Shh might promote leukocytes extravasation into the brain parenchyma.
- Subjects :
- 0301 basic medicine
CD4-Positive T-Lymphocytes
T cell
Major histocompatibility complex
03 medical and health sciences
0302 clinical medicine
astrocyte
Antigens, CD
medicine
Cytotoxic T cell
Humans
Ectonucleotidase
Immune response
5'-Nucleotidase
Neuroinflammation
Glia limitans
calcium
immunosuppression
biology
Research Paper: Immunology
Immunity
Cell Differentiation
Cell biology
Up-Regulation
030104 developmental biology
medicine.anatomical_structure
Oncology
Astrocytes
Immunology
biology.protein
Immunology and Microbiology Section
Signal transduction
030217 neurology & neurosurgery
Astrocyte
Signal Transduction
ectonucleotidase
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....cb377190ecc762935c172c4889ce77e6