Abstract T P97: CCL17-deficiency Leads to Worsened Functional Outcome and Increased Lesion Size in Experimental Stroke
Introduction: Progression of post-stroke tissue damage is partially driven by an inflammatory response involving different subsets of innate and adaptive immune cells. Functionally diverse T-cell subsets have been associated with beneficial and deleterious effects in lesion development. The role of dendritic cells (DCs), which are crucial for T-cell activation, remains undetermined so far. DCs, which express the CC-chemokine CCL17 are key regulators of Treg- and Th17-cell function. The role of DC-dependent immunomodulation as well as the impact of CCL17 in the pathogenesis of cerebral ischemia has not yet been defined.
Methods: Transient middle cerebral ischemia was induced by middle cerebral artery occlusion (MCAO, 30 min) in CCL17-deficient (CCL17E/E), heterozygous (CCL17E/+) and wildtype (WT) adult mice. Following MCAO, mice were tested for functional outcome, infarct volume, CCL17 expression and presence of immune cells by immunofluorescence analysis and flow cytometry.
Results: Cerebral ischemia led to worsened functional outcome (p<0.001) and increased infarct lesion size (p<0.05) in CCL17-deficient mice. Immunofluorescence analysis of brain tissues revealed expression of CCL17 within the lesion and the ipsilateral hippocampus. CCL17-deficient brains showed enhanced neutrophil immigration, but decreased monocyte recruitment and microglial activation.
Conclusion: Altogether, these results suggest a neuroprotective role of CCL17 in the pathogenesis of ischemia/reperfusion damage.
Author Disclosures: J. Strecker: None. K. Diederich: None. A. Schmidt: None. I. Förster: None. J. Alferink: None. J. Minnerup: None.
- © 2015 by American Heart Association, Inc.