PirB negatively regulates the inflammatory activation of astrocytes in a mouse model of sleep deprivation

Immune receptors and aging brain

“…Leukocyte immunoglobulin-like receptors (LILRs), located in the neuronal compartment of the central nervous system (CNS), play crucial roles in various functions from axonal guidance in early development to age-related and pathological changes affecting synaptic strength [ 1 , 3 , 16 , 30 , 80 ]. The LILR genes are part of the leukocyte receptor complex region on human chromosome 19, which contains several receptors related to the immunoglobulin (Ig) superfamily, including killer Ig-like receptors [ 81 ].…”

“…The function of LILRB2 in the brain has been particularly well explored via its mouse homologue, PIRB [ 1 , 3 , 16 , 33 , 52 , 80 ]. In mouse brains, PIRB is found in neurons in cerebral cortex, hippocampus, cerebellum, olfactory bulbs, retina [ 1 , 30 , 33 , 34 , 44 , 52 , 91–96 ].…”

“…In addition to aging and AD leading to increase in protein levels of both LILRB2 receptor [ 97 ] and its ligands [ 97 , 103 ], many pathological conditions further exacerbate this process, raising the probability of excessive excitatory synaptic weakening and removal via LILRB2 [ 1 , 3 , 80 , 91 , 95 , 96 , 111 , 115–118 ] ( Figure 1 ). In MCAO mouse model of stroke, the expression of PIRB and its MHC-I ligands (H2-K and H2-D), go up and peak at around 7-day post-reperfusion [ 44 , 91 ]; the elevation in all three proteins appears to be neuronal [ 91 ], suggesting that previously described role for MHC-I and PIRB in promoting LTD [ 12 , 16 , 33 , 52 ] can contribute to the pathological synapse loss in the ischemic penumbra around the infarct zone.…”