2.50
Hdl Handle:
http://hdl.handle.net/10033/322904
Title:
Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia.
Authors:
Prajeeth, Chittappen K; Löhr, Kirsten; Floess, Stefan; Zimmermann, Julian; Ulrich, Reiner; Gudi, Viktoria; Beineke, Andreas; Baumgärtner, Wolfgang; Müller, Marcus; Huehn, Jochen; Stangel, Martin
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.
Journal:
Brain, behavior, and immunity
Issue Date:
Mar-2014
URI:
http://hdl.handle.net/10033/322904
DOI:
10.1016/j.bbi.2014.01.001
PubMed ID:
24412213
Type:
Article
Language:
en
ISSN:
1090-2139
Appears in Collections:
publications of the division experimentelle Immunologie (EXIM)

Full metadata record

DC FieldValue Language
dc.contributor.authorPrajeeth, Chittappen Ken
dc.contributor.authorLöhr, Kirstenen
dc.contributor.authorFloess, Stefanen
dc.contributor.authorZimmermann, Julianen
dc.contributor.authorUlrich, Reineren
dc.contributor.authorGudi, Viktoriaen
dc.contributor.authorBeineke, Andreasen
dc.contributor.authorBaumgärtner, Wolfgangen
dc.contributor.authorMüller, Marcusen
dc.contributor.authorHuehn, Jochenen
dc.contributor.authorStangel, Martinen
dc.date.accessioned2014-07-14T14:20:28Z-
dc.date.available2014-07-14T14:20:28Z-
dc.date.issued2014-03-
dc.identifier.citationEffector molecules released by Th1 but not Th17 cells drive an M1 response in microglia. 2014, 37:248-59 Brain Behav. Immun.en
dc.identifier.issn1090-2139-
dc.identifier.pmid24412213-
dc.identifier.doi10.1016/j.bbi.2014.01.001-
dc.identifier.urihttp://hdl.handle.net/10033/322904-
dc.description.abstractMicroglia 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.en
dc.language.isoenen
dc.rightsArchived with thanks to Brain, behavior, and immunityen
dc.titleEffector molecules released by Th1 but not Th17 cells drive an M1 response in microglia.en
dc.typeArticleen
dc.identifier.journalBrain, behavior, and immunityen

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