CD93/AA4.1: A Novel Regulator of Inflammation in Murine Focal Cerebral Ischemia

Abstract

International audienceThe stem-cell marker CD93 (AA4.1/C1qRp) has been described as a potential complement C1q-receptor. Its exact molecular function, however, remains unknown. By using global expression profiling we showed that CD93-mRNA is highly induced after transient focal cerebral ischemia. CD93 protein is upregulated in endothelial cells, but also in selected macrophages and microglia. To elucidate the potential functional role of CD93 in postischemic brain damage, we used mice with a targeted deletion of the CD93 gene. After 30 min of occlusion of the middle cerebral artery and 3 d of reperfusion these mice displayed increased leukocyte infiltration into the brain, increased edema, and significantly larger infarct volumes (60.8 ± 52.2 versus 23.9 ± 16.6 mm3) when compared with wild-type (WT) mice. When the MCA was occluded for 60 min, after 2 d of reperfusion the CD93 knockout mice still showed more leukocytes in the brain, but the infarct volumes were not different from those seen in WT animals. To further explore CD93-dependent signaling pathways, we determined global transcription profiles and compared CD93-deficient and WT mice at various time points after induction of focal cerebral ischemia. We found a highly significant upregulation of the chemokine CCL21/Exodus-2 in untreated and treated CD93-deficient mice at all time points. Induction of CCL21 mRNA and protein was confirmed by PCR and immunohistochemistry. CCL21, which was formerly shown to be released by damaged neurons and to activate microglia, contributes to neurodegeneration. Thus, we speculate that CD93-neuroprotection is mediated via suppression of the neuroinflammatory response through downregulation of CCL21

Elevated Expression of the C-Type Lectin CD93 in the Glioblastoma Vasculature Regulates Cytoskeletal Rearrangements That Enhance Vessel Function and Reduce Host Survival

“…The linkage of CD93 to the actin cytoskeleton is also essential for its previously described role in phagocytosis (22,32). Previous studies have pointed to a role for CD93 in leukocyte infiltration in various inflammatory models (33,34). However, we did not detect any difference in leukocyte infiltration into GL261 and T241 tumors between CD93-deficient and wild-type mice ( Supplementary Fig.…”

Knockout of Silent Information Regulator 2 (SIRT2) Preserves Neurological Function after Experimental Stroke in Mice

“…RNA derived from the separated hemispheres, pooled from six wild-type C57Bl/6 mice (after MCAO or sham treatment) at each time point, were used for gene expression analysis using Affymetrix GeneChip Mouse Expression Set 430 (Affymetrix, Santa Clara, CA, USA) as described previously. 15,16 To determine the induction of specific mRNAs in the ischemic hemispheres of MCAO-treated animals, expression values were compared with those derived from sham-operated animals. Commercially available Affymetrix software was applied for data analysis of the Affymetrix GeneChips.…”

Helicobacter pylori Infection Increases Frequency of PDCA-1+ (CD317+) B-cell Subsets

“…Cells labeled by CD93 were increased in patients with HP infection, and this subset has been associated with the development of angiogenesis and tumor growth. According to the current body of biomedical literature, the higher frequency of CD93 þ PDCA-1 þ B cells and CD93þPDCA-1þIgMþ B cells may contribute to the development of further symptomatic episodes and deterioration of patient condition (14,15). Nevertheless, CD137, which is constitutively expressed on PDCA-1 þ B cells, is believed to negatively modulate the humoral immune response, and PDCA-1 þ B cells may have a phenotypic overlap with Bregs.…”

“…CD137 is generally known as an important T-cell activating molecule but also stimulates generation of the PDCA-1 þ B cell subset (13). CD93, as a relative unusual B-lymphocyte surface marker, appeared to label cells cardinal in the regulation of cell survival, migration, and angiogenesis in infectious processes (14,15). As this subset is characterized by production of type I IFNs, which are prominent mediators of immune response against bacteria and viruses (16) and play a cardinal role in priming humoral responses (17), it is possible that it is involved in H. pylori infection.…”