ミクログリアにおける免疫チェックポイント分子LAG-3の発現および機能解析

抄録

Microglia are resident innate immune cells in the central nervous system (CNS) and play important roles in the development of CNS homeostasis. In several CNS disorders, excessive activation and neurotoxicity of microglia are observed, but the mechanisms that regulate their activation are still unclear. Immune checkpoint molecules (e.g., PD-1, LAG-3) are expressed on activated immune cells and regulate their activation in peripheral immunity. We hypothesized that immune checkpoint molecules could also contribute to the regulation of microglial activation.

First, we analyzed the expression of immune checkpoint molecules in activated microglia using BV2, a mouse microglia cell line. We found that BV2 activated by IFN-γ expressed LAG-3 and the STAT1 signaling pathway was involved in the expression of LAG-3. To investigate the function of LAG-3 in activated microglia, we treated IFN-γ-activated BV2 with an antagonistic anti-LAG-3 antibody to inhibit LAG-3 function. The result showed that the inhibition of LAG-3 increased nitric oxide (NO) production upon IFN-γ activation, indicating that LAG-3 could be suppressing microglial activation.

Our results suggest that activated microglia express LAG-3 and that LAG-3 could function as a negative feedback mechanism to regulate microglial activation.