Brief exposure to hyperglycemia activates dendritic cells in vitro and in vivo

• Type of Material: Article
• Authors: Aline M Thomas, Georgia Institute of Technology; Ying Dong, Emory University; Nicolas M Beskid, Georgia Institute of Technology; Andrés J Garcia, Georgia Institute of Technology; Andrew Adams, Emory University; Julia Babensee, Emory University
• Language: English
• Date: 2019-11-01
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Wiley Periodicals, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1002/jcp.29380
• Title of Journal or Parent Work: JOURNAL OF CELLULAR PHYSIOLOGY
• Volume: 235
• Issue: 6
• Start Page: 5120
• End Page: 5129
• Grant/Funding Information: This work was supported by NIH (ACTSI, UL1TR000454; 1 R21 EB019166–01A1), Georgia Partner’s Regenerative Medicine (REM) seed grant, and Georgia Immunoengineering Consortium’s seed grant.; The first author received support from the ILET2 training grant (1 R90 DK098981, 1 T90 DK097787)
• Keywords: immunity; MACROPHAGES; T-CELLS; Physiology; Science & Technology; NONOBESE DIABETIC MOUSE; GLUCOSE; diabetes; B-CELLS; hyperglycemia; INFLAMMATION; MICE; DIFFERENTIATION; dendritic cells; Life Sciences & Biomedicine; interleukin-10; hydrogel; ANTIGEN PRESENTATION; Cell Biology; NECROSIS-FACTOR-ALPHA

Abstract

Dendritic cells are key players in regulating immunity. These cells both activate and inhibit the immune response depending on their cellular environment. Their response to hyperglycemia, a condition common amongst diabetics wherein glucose is abnormally elevated, remains to be elucidated. In this study, the phenotype and immune response of dendritic cells exposed to hyperglycemia were characterized in vitro and in vivo using the streptozotocin-induced diabetes model. Dendritic cells were shown to be sensitive to hyperglycemia both during and after differentiation from bone marrow precursor cells. Dendritic cell behavior under hyperglycemic conditions was found to vary by phenotype, among which, tolerogenic dendritic cells were particularly sensitive. Expression of the costimulatory molecule CD86 was found to reliably increase when dendritic cells were exposed to hyperglycemia. Additionally, hydrogel-based delivery of the anti-inflammatory molecule interleukin-10 was shown to partially inhibit these effects in vivo.