Loading...
Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia.
Prajeeth, Chittappen K Löhr, Kirsten Floess, Stefan Zimmermann, Julian Ulrich, Reiner Gudi, Viktoria Beineke, Andreas Baumgärtner, Wolfgang Müller, Marcus Huehn, Jochen
Prajeeth, Chittappen K
Löhr, Kirsten
Floess, Stefan
Zimmermann, Julian
Ulrich, Reiner
Gudi, Viktoria
Beineke, Andreas
Baumgärtner, Wolfgang
Müller, Marcus
Huehn, Jochen
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2014-03
Submitted date
Files
Loading...
original manuscript
Adobe PDF, 1.01 MB
Other Titles
Abstract
Microglia act as sensors of inflammation in the central nervous system (CNS) and respond to many stimuli. Other key players in neuroinflammatory diseases are CD4+ T helper cell (Th) subsets that characteristically secrete IFN-γ (Th1) or IL-17 (Th17). However, the potential of a distinct cytokine milieu generated by these effector T cell subsets to modulate microglial phenotype and function is poorly understood. We therefore investigated the ability of factors secreted by Th1 and Th17 cells to induce microglial activation. In vitro experiments wherein microglia were cultured in the presence of supernatants derived from polarized Th1 or Th17 cultures, revealed that Th1-associated factors could directly activate and trigger a proinflammatory M1-type gene expression profile in microglia that was cell-cell contact independent, whereas Th17 cells or its associated factors did not have any direct influence on microglia. To assess the effects of the key Th17 effector cytokine IL-17A in vivo we used transgenic mice in which IL-17A is specifically expressed in astrocytes. Flow cytometric and histological analysis revealed only subtle changes in the phenotype of microglia suggesting only minimal effects of constitutively produced IL-17A on microglia in vivo. Neither IL-23 signaling nor addition of GM-CSF, a recently described effector molecule of Th17 cells, changed the incapacity of Th17 cells to activate microglia. These findings demonstrate a potent effect of Th1 cells on microglia, however, the mechanism of how Th17 cells achieve their effect in CNS inflammation remains unclear.
Citation
Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia. 2014, 37:248-59 Brain Behav. Immun.
Affiliation
Publisher
Journal
PubMed ID
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
1090-2139
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Archived with thanks to Brain, behavior, and immunity