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.