Depletion of CD11c⁺ Cells Does Not Influence Outcomes in Mice Subjected to Transient Middle Cerebral Artery Occlusion

Abstract

Objective: While it has been shown that different T-cell subsets have a detrimental role in the acute phase of ischemic stroke, data on the impact of dendritic cells (DC) are missing. Classic DC can be characterized by the cluster of differentiation (CD)11c surface antigen. Methods: In this study, we depleted CD11c⁺ cells by using a CD11c-diphtheria toxin (DTX) receptor mouse strain that allows selective depletion of CD11c⁺ cells by DTX injection. For stroke induction, we used the model of transient middle cerebral artery occlusion (tMCAO) and analyzed stroke volume and functional outcome on days 1 and 3 as well as expression of prototypical pro- and anti-inflammatory cytokines on day 1 after tMCAO. Three different protocols for CD11c⁺ cell depletion, tMCAO duration, and readout time point were applied. Results: Injection of DTX (5 or 100 ng/g) reliably depleted CD11c⁺ cells without influencing the fractions of other immune cell subsets. CD11c⁺ cell depletion had no impact on stroke volume, but mice with a longer DTX pretreatment performed worse than those with vehicle treatment. CD11c⁺ cell depletion led to a decrease in cortical interleukin (IL)-1β and IL-6 messenger ribonucleic acid levels. Conclusions: We show, for the first time, that CD11c⁺ cell depletion does not influence stroke volume in a mouse model of focal cerebral ischemia. Nevertheless, given the unspecificity of the CD11c surface antigen for DC, mouse models that allow a more selective depletion of DC are needed to investigate the role of DC in stroke pathophysiology.