Fig. 7.

Decreased astrocyte-associated expression of miR-221 and miR-222 in mTLE + HS. a, d Scatter plots of log² Hy3/Hy5 ratios for miR-221 and miR-222. Triangles represent individual patients and gray horizontal bars group means. b, c, e, f miRNA-ISH combined with immunofluorescent labeling for glial fibrillary acidic protein (GFAP). The miRNA-ISH signal is pseudocolored in green, nuclear DAPI staining in blue and GFAP labeling in red. The right part of each panel shows images of individual astrocytes at a higher magnification. miR-221 and miR-222 are detected in GFAP-positive astrocytes in controls (not shown) and mTLE−HS patients (b, e). In contrast, expression of miR-221 and miR-222 is absent or weak in astrocytes of the mTLE + HS hippocampus (c, f). g Hypothetical model of miRNA-regulated expression of ICAM1 in astrocytes in mTLE. In mTLE + HS, expression of miR-221 and miR-222 is down-regulated in astrocytes in the hippocampus as compared to control. These miRNAs target the 3′UTR of ICAM1 and reduce ICAM1 expression. Therefore, reduced miR-221 and miR-222 expression in mTLE + HS may induce enhanced astrocyte-associated expression of ICAM1. In line with this model, ICAM1 protein expression is increased in astrocytes in mTLE + HS patients. Astrocyte-associated ICAM1 has been associated with the recruitment, accumulation, and activation of leukocytes and microglia. These cells express ICAM1-binding partners such as LFA-1 and Mac-1 and ICAM1-LFA-1/Mac-1 interactions can trigger the production of inflammatory mediators by astrocytes and immune cells. These effects may contribute to the enhanced and sustained immune response observed in the mTLE + HS hippocampus. The signals that trigger changes in astrocyte-associated miRNA expression are unknown but may include factors such as IFN-γ, which can regulate ICAM1 expression at the post-transcriptional level. Scale bar 40 μm