Characterization of the Leucocyte Immunoglobulin-like Receptor B4 (Lilrb4) Expression in Microglia

Simple Summary: In the present study, we provide a detailed characterization of Lilrb4 expression in microglia and peripheral myeloid cells. Our data demonstrate that LILRB4 is a marker for microglia activation, as evidenced by upregulation after lipopolysaccharide treatment and inhibition of microglial TGF beta signaling. Moreover, we provide evidence that microglia express low levels of Lilrb4 in vivo and high levels in vitro, and we clearly demonstrate that LILRB4 is also expressed by bone marrow-derived monocytes and, to a greater extent, by peritoneal macrophages, defining LILRB4 as a surface marker of myeloid cells and not as a microglia-specific marker. As resident innate immune cells of the CNS, microglia play important essential roles during physiological and pathological situations. Recent reports have described the expression of Lilrb4 in disease-associated and aged microglia. Here, we characterized the expression of Lilrb4 in microglia in vitro and in vivo in comparison with bone marrow-derived monocytes and peritoneal macrophages in mice. Using BV2 cells, primary microglia cultures as well as ex vivo isolated microglia and myeloid cells in combination with qPCR and flow cytometry, we were able to provide a comprehensive characterization of Lilrb4 expression in distinct mouse myeloid cells. Whereas microglia in vivo display low expression of Lilrb4, primary microglia cultures present high levels of surface LILRB4. Among the analyzed peripheral myeloid cells, peritoneal macrophages showed the highest expression levels of Lilrb4. Moreover, LPS treatment and inhibition of microglial TGF beta signaling resulted in significant increases of LILRB4 cell surface levels. Taken together, our data indicate that LILRB4 is a reliable surface marker for activated microglia and further demonstrate that microglial TGF beta signaling is involved in the regulation of Lilrb4 expression during LPS-induced microglia activation.

Automated summary

This study provides a detailed characterization of Lilrb4 expression in microglia and peripheral myeloid cells, demonstrating that LILRB4 is a surface marker for activated microglia. The research also shows that microglial TGF beta signaling is involved in regulating Lilrb4 expression during LPS-induced microglia activation.