Ectonucleotidase activity and immunosuppression in astrocyte-CD4 T cell bidirectional signaling

Oncotarget
Fabia FilipelloFabio Grassi

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 duri...Continue Reading

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Citations

Mar 5, 2016·Journal of Leukocyte Biology·Tanja Rezzonico JostFabio Grassi
Mar 2, 2018·Journal of Dental Research·T OuchiS Asoda
Jun 3, 2021·International Journal of Molecular Sciences·Rina AharoniRuth Arnon
Jul 23, 2021·The Journal of Experimental Medicine·Liliana M SanmarcoFrancisco J Quintana

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Methods Mentioned

BETA
flow cytometry
reverse transcription PCR
ELISA
FACS

Software Mentioned

ImageJ
FlowJo
- Pad
MetaFluor
Graph
GraphPad Prism

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