CD93 regulates central nervous system inflammation in two mouse models of autoimmune encephalomyelitis. Issue 3 (11th July 2018) - Griffiths, Mark R.
Summary: Microglia and non‐professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue debris in the injured central nervous system through major pro‐inflammatory processes. However, the mechanisms involved in regulating these responses remain ill‐characterized. We herein show that CD93, also known as complement C1qRp/AA4 stem cell marker, has an important role in the regulation of inflammatory processes. The role of CD93 was evaluated in two models of neuroinflammation. We used the MOG‐experimental autoimmune encephalomyelitis (EAE) model and the antibody‐dependent EAE (ADEAE), which were induced in wild‐type and CD93 knockout mice. We found that CD93 was highly expressed by neurons, endothelial cells and microglia (ramified >> amoeboid). Astrocytes and oligodendrocytes did not to express CD93. We further observed that CD93‐deficient (CD93 −/− ) mice presented a more robust brain and spinal cord inflammation in EAE and ADEAE. Encephalitis in CD93 −/− was characterized by increased numbers of infiltrating M1 macrophages (CD11c + CD206 − ) and amoeboid microglia exhibiting a more activated phenotype (Tomato Lectin high Cox2 high ). Damage to and leakage through the blood–brain barrier was increased in CD93 −/− animals and was associated with a more robust neuronal injury when compared with wild‐type EAE mice. We propose that CD93 is an important neuro‐immune regulator to control central nervous system inflammation. Abstract : CD93, C‐type‐like lectin is highly expressed by endothelial cells, microglia and neurons in the central nervous system. The inflammatory response induced in experimental autoimmune encephalomyelitis and antibody‐dependent EAE models is more severe in CD93‐deficient mice. Neuronal apoptosis and blood–brain barrier (BBB) damage are more pronounced in CD93‐deficient mice.