Central nervous system pericytes express soluble ST2 in inflammation and injury

Abstract Brain pericytes are mediators of neuroinflammation, as evidenced in vitro, in animal models and humans. We and others have identified the platelet-derived growth factor (PDGF)-BB -PDGF receptor beta (PDGFRB) pathway as a key modulator of inflammatory cues in human brain pericytes. We investigate the receptor for interkeukin-33 (IL-33), interkeukin-1 receptor-like 1 (IL1RL1; also known as ST2) as a highly upregulated transcript in response to PDGF-BB stimulation in pericyte cultures. We show that pericytes express transcripts for both the membrane bound form of the receptor (ST2L) and the soluble form (sST2) that acts as a decoy and blocks IL-33 signalling. Human brain pericytes secrete sST2 in response to PDGF-BB, but also to transforming growth factor alpha (TGF) alpha and interleukin-4 (IL-4), although they are unresponsive to IL-33 treatment. We also examine pericyte expression of both IL1RL1 transcripts using RNAscope in two different in vivo models of neuroinflammation, experimental autoimmune encephalitis (EAE) and photothrombotic stroke. We present data showing that in rodents pericytes increase transcript expression predominantly for soluble IL1RL1 in inflammatory and stroke models. Our results highlight a novel expression pattern of the soluble and membrane bound forms of the IL-33 receptor in vitro and in combination with our observations in vivo suggest that cerebrovascular pericytes may negatively regulate IL-33 signalling following injury or inflammatory insults to the brain.