CD84 Links T Cell and Platelet Activity in Cerebral Thrombo-inflammation in Acute Stroke

 

Stroke is the third leading cause of death following diseases of the heart and cancer. A majority of strokes are classified as ischemic in nature (87%), with intracerebral hemorrhagic (10%) and subarachnoid hemorrhagic (3%) accounting for the rest. Recanalization of the occluded brain arteries in acute ischemic strokes is essential but not sufficient to guarantee brain salvage. Infarcts often develop further due to a thrombo-inflammatory process critically involving platelets and T cells; however, the underlying mechanisms are unknown. CD84 is a member of the signaling lymphocyte activation molecule (SLAM) family, which includes homophilic and heterophilic receptors that modulate both adaptive and innate immune responses. CD84 acts as a homophilic cell adhesion molecule highly expressed on platelets and on different immune cell populations, where it serves as a co-receptor. David Stegner, Ph.D., of the University of Würzburg in Germany aimed to assess the potential contribution that CD84 had on infarct growth following experimental stroke. Findings could suggest a pharmacologic target aimed toward managing patients suffering from an ischemic stroke.

Stegner presented on Sunday, during the Platelets and Megakaryocytes virtual session, findings from mice that were lacking CD84 either constitutively or on their platelets. Mice were subjected to the transient middle cerebral artery occlusion (tMCAO) model and to subsequent examination of their infarct sizes. Results demonstrated that Cd84−/− mice, as well as mice lacking CD84 on either platelets or T cells, displayed reduced cerebral CD4+ T-cell infiltration following experimental stroke. This ultimately resulted in reduced neurological damage. In vitro, CD84 either derived from activated platelets or added as recombinant protein enhanced the motility of WT but not of Cd84/ T cells.

These data from animal studies were supported by a small prospective cohort study revealing that high platelet CD84 expression levels were associated with poor outcome in stroke patients. Stegner was able to ascertain from these findings that indeed CD84 should serve as a potential pharmacologic target.

Read the full abstract here.

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