Details

Autor(en) / Beteiligte

• Gelderblom, Mathias
• Gallizioli, Mattia
• Ludewig, Peter
• Thom, Vivien
• Arunachalam, Priyadharshini
• Rissiek, Björn
• Bernreuther, Christian
• Glatzel, Markus
• Korn, Thomas
• Arumugam, Thiruma Valavan
• Sedlacik, Jan
• Gerloff, Christian
• Tolosa, Eva
• Planas, Anna M
• Magnus, Tim

Titel

IL-23 (Interleukin-23)–Producing Conventional Dendritic Cells Control the Detrimental IL-17 (Interleukin-17) Response in Stroke

Ist Teil von

• Stroke (1970), 2018-01, Vol.49 (1), p.155-164

Ort / Verlag

United States: American Heart Association, Inc

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• BACKGROUND AND PURPOSE—Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ and γδ T cells are established mediators of tissue damage in stroke, and the role of dendritic cells (DCs) in inducing the early events of T cell activation and differentiation in stroke is not well understood. METHODS—In a murine model of experimental stroke, we defined the immune phenotype of infiltrating DC subsets based on flow cytometry of surface markers, the expression of ontogenetic markers, and cytokine levels. We used conditional DC depletion, bone marrow chimeric mice, and IL-23 (interleukin-23) receptor-deficient mice to further explore the functional role of DCs. RESULTS—We show that the ischemic brain was rapidly infiltrated by IRF4/CD172a conventional type 2 DCs and that conventional type 2 DCs were the most abundant subset in comparison with all other DC subsets. Twenty-four hours after ischemia onset, conventional type 2 DCs became the major source of IL-23, promoting neutrophil infiltration by induction of IL-17 (interleukin-17) in γδ T cells. Functionally, the depletion of CD11c cells or the genetic disruption of the IL-23 signaling abrogated both IL-17 production in γδ T cells and neutrophil infiltration. Interruption of the IL-23/IL-17 cascade decreased infarct size and improved neurological outcome after stroke. CONCLUSIONS—Our results suggest a central role for interferon regulatory factor 4-positive IL-23–producing conventional DCs in the IL-17–dependent secondary tissue damage in stroke.