Adoptive transfer of GRP78-treated dendritic cells alleviates insulitis in NOD mice. Issue 6 (13th October 2021)

• Record Type: Journal Article
• Authors: Zhou, Xiaoqi; Yang, Muyang; Lv, Yibing; Li, Heli; Wu, Sha; Min, Jie; Shen, Guanxin; He, Yong; Lei, Ping
• Is Part Of: Journal of leukocyte biology. Volume 110:Issue 6(2021)
• Page Start: 1023
• Page End: 1031
• Publication Date: 2021-10-13
• Subjects: glucose-regulated protein 78 -- NOD mice -- RAMPs -- tolerogenic dendritic cells -- type 1 diabetes; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.3MA0921-219RRRR
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: The 78-kDa glucose-regulated protein (GRP78) has extracellular, anti-inflammatory properties that can aid resolving inflammation. It has been established previously that GRP78 induced myeloid CD11c + cell differentiation into distinct tolerogenic cells. This tolerance induction makes GRP78 a potential therapeutic agent for transplanted allogeneic grafts and autoimmune diseases, such as type 1 diabetes. In this research, it is revealed that rmGRP78-treated NOD mice bone marrow-derived CD11c + cells (GRP78-DCs) highly expressed B7-H4 but down-regulated CD86 and CD40, and retained a tolerogenic signature even after stimulation by LPS. In the assessment of in vivo therapeutic efficacy after the adoptive transfer of GRP78-DCs into NOD mice, fluorescent imaging analyses revealed that the transfer specifically homed in inflamed pancreases, promoting β-cell survival and alleviating insulitis in NOD mice. The adoptive transfer of GRP78-DCs also helped reduce Th1, Th17, and CTL, suppressing inflammatory cytokine production in vivo. The findings suggest that adoptive GRP78-DC transfer is critical to resolving inflammation in NOD mice and may have relevance in a clinical setting. Graphical Abstract: Adoptively transferred GRP78-DCs, specifically homed to the inflamed pancreas, can promote beta cell survival, alleviate insulitis, and resolve inflammation in NOD mice.