Adoptive transfer of GRP78-treated dendritic cells alleviates insulitis in NOD mice
| Autor: | Jie Min, Guanxin Shen, Sha Wu, Xiaoqi Zhou, Yong He, Muyang Yang, Heli Li, Ping Lei, Yibing Lv |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adoptive cell transfer
medicine.medical_treatment Immunology Islets of Langerhans Mice Mice Inbred NOD Immune Tolerance medicine Animals Immunology and Allergy Endoplasmic Reticulum Chaperone BiP NOD mice CD86 CD40 biology Cell Differentiation hemic and immune systems Dendritic Cells Cell Biology medicine.disease Adoptive Transfer Tolerance induction CTL Diabetes Mellitus Type 1 Cytokine Pancreatitis biology.protein Female Insulitis |
| Zdroj: | Journal of Leukocyte Biology. 110:1023-1031 |
| ISSN: | 1938-3673 0741-5400 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text