title: Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia.
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.
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Chittappen K
authors.initials: CK
authors.lastname: Prajeeth
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Löhr
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Floess
authors.affiliation: Department of Neurology, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Julian
authors.initials: J
authors.lastname: Zimmermann
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gudi
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hannover, Bünteweg 17, D-30559 Hannover, Germany; Center of Systems Neuroscience, Hannover, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.affiliation: Department of Neurology, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Müller
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Inhoffenstr. 7, D-38124 Braunschweig, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
authors.affiliation: Clinical Neuroimmunology and Neurochemistry, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany; Center of Systems Neuroscience, Hannover, Germany. Electronic address: stangel.martin@mh-hannover.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Stangel
mesh_terms: D000818:Animals; D020381:Interleukin-17 / Q000378:metabolism; D053760:Interleukin-23 Subunit p19 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*
chemical_list: C098680:Il17a protein, mouse; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053760:Interleukin-23 Subunit p19
keywords: Microglia; Th1; Th17