| First Author | Schonblum A | Year | 2024 |
| Journal | J Clin Invest | Volume | 134 |
| Issue | 14 | PubMed ID | 38885342 |
| Mgi Jnum | J:357389 | Mgi Id | MGI:7665989 |
| Doi | 10.1172/JCI179335 | Citation | Schonblum A, et al. (2024) Beneficial islet inflammation in health depends on pericytic TLR/MyD88 signaling. J Clin Invest 134(14) |
| abstractText | While inflammation is beneficial for insulin secretion during homeostasis, its transformation adversely affects beta cells and contributes to diabetes. However, the regulation of islet inflammation for maintaining glucose homeostasis remains largely unknown. Here, we identified pericytes as pivotal regulators of islet immune and beta cell function in health. Islets and pancreatic pericytes express various cytokines in healthy humans and mice. To interfere with the pericytic inflammatory response, we selectively inhibited the TLR/MyD88 pathway in these cells in transgenic mice. The loss of MyD88 impaired pericytic cytokine production. Furthermore, MyD88-deficient mice exhibited skewed islet inflammation with fewer cells, an impaired macrophage phenotype, and reduced IL-1beta production. This aberrant pericyte-orchestrated islet inflammation was associated with beta cell dedifferentiation and impaired glucose response. Additionally, we found that Cxcl1, a pericytic MyD88-dependent cytokine, promoted immune IL-1beta production. Treatment with either Cxcl1 or IL-1beta restored the mature beta cell phenotype and glucose response in transgenic mice, suggesting a potential mechanism through which pericytes and immune cells regulate glucose homeostasis. Our study revealed pericyte-orchestrated islet inflammation as a crucial element in glucose regulation, implicating this process as a potential therapeutic target for diabetes. |
