RNA-seq analysis of human primary monocytes after fibrinogen stimulation with or without a LILRA2-blocking antibody.
The leukocyte immunoglobulin-like receptor (LILR) family is a group of primate-specific immunoreceptors, widely expressed on most immune cells, and regulates immune responses through interactions with various ligands. The inhibitory type, LILRB, has been widely studied, and many ligands, such as HLA class I, have been identified. However, little is known about the activating type, LILRA. We have previously identified microbially cleaved immunoglobulin as a non-self-ligand for LILRA2. Here, we identified fibrinogen as an endogenous ligand for LILRA2 using mass spectrometry. LILRA2, upon recognizing solid-phase fibrinogen, activated human primary monocytes and promoted the expression of various inflammation-related genes, such as chemokines, as revealed by RNA-seq analysis. A blocking antibody against LILRA2 completely inhibited the fibrinogen-induced inflammatory responses, indicating that LILRA2 is the major receptor of fibrinogen.