β₂ microglobulin promotes pericyte proliferation through toll-like receptor 4

Pericytes are perivascular cells that contribute to maintaining vascular integrity and central nervous system homeostasis. β₂-microglobulin (B2M) is a component of the major histocompatibility complex class I molecule; it has recently been implicated in age-related and injury-associated inflammation. Here, we investigated the phenotypic and transcriptomic effects of B2M on mouse brain pericytes in vitro. B2M treatment increased Bromodeoxyuridine (BrdU) incorporation into the cultured pericytes as well as the number of Ki67-positive pericytes. Morphologically, B2M promoted pericyte extension. Toll-like receptor 4 (TLR4), one of the key molecules that regulates B2M function, was involved in the B2M-dependent pericyte proliferation. These findings were consistent with RNA-seq results showing differential expression of genes related to cell proliferation. These results suggest that B2M directly acts on pericytes and regulates part of their functional responses through TLR4 signaling.