Paired immunoglobulin-like type 2 receptor alpha (PILRA) binds to multiple ligands including CD99 (Shiratori et al. 2004), PILR-associating neural protein (PIANP, PANP) (Kogure et al. 2011), Herpes simplex virus-1 glycoprotein B (Satoh et al. 2008), Collectin-12 (COLEC12), Neural proliferation differentiation and control protein 1 (NPDC1) and C-type lectin domain family 4 member G (CLEC4G) (Sun et al. 2012). Binding studies suggest that PILR recognizes a complex ligand domain involving both silica acid and protein motif(s). Thus, PILR is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILR ligands are expressed. The precise function of PILRa-Ligand interaction is not well understood (Sun et al. 2012).
PILRa negatively regulates inflammation and keeps myeloid system in check. Pilra KO mice produce more pathogenic cytokines during inflammation and are prone to enhanced autoimmune arthritis. Correspondingly, anti-PILRa mAb ameliorated inflammation in mouse arthritis models and suppressed the production of proinflammatory cytokines (Sun et al. 2014).