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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties

Authors: Chittappen K. Prajeeth, Julius Kronisch, Reza Khorooshi, Benjamin Knier, Henrik Toft-Hansen, Viktoria Gudi, Stefan Floess, Jochen Huehn, Trevor Owens, Thomas Korn, Martin Stangel

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Autoreactive Th1 and Th17 cells are believed to mediate the pathology of multiple sclerosis in the central nervous system (CNS). Their interaction with microglia and astrocytes in the CNS is crucial for the regulation of the neuroinflammation. Previously, we have shown that only Th1 but not Th17 effectors activate microglia. However, it is not clear which cells are targets of Th17 effectors in the CNS.

Methods

To understand the effects driven by Th17 cells in the CNS, we induced experimental autoimmune encephalomyelitis in wild-type mice and CD4+ T cell-specific integrin α4-deficient mice where trafficking of Th1 cells into the CNS was affected. We compared microglial and astrocyte response in the brain and spinal cord of these mice. We further treated astrocytes with supernatants from highly pure Th1 and Th17 cultures and assessed the messenger RNA expression of neurotrophic factors, cytokines and chemokines, using real-time PCR. Data obtained was analyzed using the Kruskal-Wallis test.

Results

We observed in α4-deficient mice weak microglial activation but comparable astrogliosis to that of wild-type mice in the regions of the brain populated with Th17 infiltrates, suggesting that Th17 cells target astrocytes and not microglia. In vitro, in response to supernatants from Th1 and Th17 cultures, astrocytes showed altered expression of neurotrophic factors, pro-inflammatory cytokines and chemokines. Furthermore, increased expression of chemokines in Th1- and Th17-treated astrocytes enhanced recruitment of microglia and transendothelial migration of Th17 cells in vitro.

Conclusion

Our results demonstrate the delicate interaction between T cell subsets and glial cells and how they communicate to mediate their effects. Effectors of Th1 act on both microglia and astrocytes whereas Th17 effectors preferentially target astrocytes to promote neuroinflammation.
Appendix
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Metadata
Title
Effectors of Th1 and Th17 cells act on astrocytes and augment their neuroinflammatory properties
Authors
Chittappen K. Prajeeth
Julius Kronisch
Reza Khorooshi
Benjamin Knier
Henrik Toft-Hansen
Viktoria Gudi
Stefan Floess
Jochen Huehn
Trevor Owens
Thomas Korn
Martin Stangel
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0978-3

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