Transcriptomic analysis reveals that IL-1R8/Sigirr is a novel macrophage migration regulator and suppresses macrophage proliferation through p38 MAPK signaling pathway

Abstract

IL-1R8, also known as the Single immunoglobin interleukin-1 (IL-1)-related receptor (Sigirr), has been demonstrated as a negative regulator of IL-1R and Toll-like receptor (TLR) downstream signaling pathways and inflammation. However, the role of IL-1R8 in macrophage migration and proliferation remains unknown. Here we investigated transcriptome profiles of WT and Il1r8-deficient splenocytes and found that innate immunity and cell migration related pathways were significantly correlated with IL-1R8 expression. Cell migration-related genes were downregulated in Il1r8−/− splenocytes or IL-1R8-depleted RAW264.7 cells. Further experiments revealed that IL-1R8-depleted RAW264.7 cells or Il1r8−/− BMDMs exhibited impaired cell migration. Moreover, we found that IL-1R8 suppresses macrophage proliferation through p38 MAPK signaling pathway. Therefore, our study suggests that IL-1R8 is a new positive regulator for macrophage migration and suppresses macrophage proliferation.