CD93 regulates CNS inflammation in two mouse models of autoimmune encephalomyelitis

Abstract

Microglia and non-professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue-debris in the injured CNS through major pro-inflammatory processes. However, the mechanisms involved in regulating these responses remain ill-characterised. 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 Lectinhigh , Cox2high ). Damage and leakage of the blood brain barrier was increased in CD93-/- animals and was associated with a more robust neuronal injury when compared to wild type EAE mice. We propose that CD93 is an important neuro-immune regulator (NIREG) to control CNS inflammation.