Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice

Young-Sun Lee, Hyuk Soo Eun, So Yeon Kim, Jong Min Jeong, Wonhyo Seo, Jin Seok Byun, Won Il Jeong, Hyon Seung Yi

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Abstract

Emerging evidence revealed that diabetes induces abnormal immune responses that result in serious complications in organs. However, the effect of hyperglycemia on hepatic immunity remains obscure. We evaluated the population and function of hepatic immune cells in streptozotocin (STZ)-induced hyperglycemic mice. CC chemokine receptor 2 (CCR2)-knockout mice and mice with a depletion of regulatory T cells (DEREG) were used to investigate the migration and role of regulatory T cells (Tregs) in hyperglycemic mice. The inflammatory cytokines and hepatic transaminase levels were significantly increased in the hyperglycemic mice. The population and number of infiltrating monocytes, granulocytes, and Tregs were enhanced in the livers of the hyperglycemic mice. Hepatic monocytes other than macrophages showed the increased expression of inflammatory cytokines and chemokines in the hyperglycemic mice. The CCR2 knockout and DEREG chimeric mice exhibited increased populations of activated T cells and neutrophils compared to the WT chimeric mice, which promoted hepatic inflammation in the hyperglycemic mice. The migration of CCR2 knockout Tregs into the liver was significantly reduced compared to the WT Tregs. We demonstrated that hyperglycemia contributes to increase in infiltrating monocytes and Tregs, which are associated with hepatic immune dysfunction in mice. CCR2-mediated migration of Tregs regulates hyperglycemia-induced hepatic inflammation.

Original languageEnglish
Article number30656
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Jul 28

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    Lee, Y-S., Eun, H. S., Kim, S. Y., Jeong, J. M., Seo, W., Byun, J. S., Jeong, W. I., & Yi, H. S. (2016). Hepatic immunophenotyping for streptozotocin-induced hyperglycemia in mice. Scientific reports, 6, [30656]. https://doi.org/10.1038/srep30656