| Autor: |
D.C. Oran, T. Lokumcu, Y. Inceoglu, M.B. Akolpoglu, O. Albayrak, T. Bal, M. Kurtoglu, M. Erkan, F. Can, T. Bagci-Onder, S. Kizilel |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Materials Today Bio, Vol 2, Iss , Pp - (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2590-0064 |
| DOI: |
10.1016/j.mtbio.2019.100006 |
| Popis: |
Type 1 diabetes (T1D) is an autoimmune disease characterized by destruction of pancreatic β cells. One of the promising therapeutic approaches in T1D is the transplantation of islets; however, it has serious limitations. To address these limitations, immunotherapeutic strategies have focused on restoring immunologic tolerance, preventing transplanted cell destruction by patients’ own immune system. Macrophage-derived chemokines such as chemokine-ligand-22 (CCL22) can be utilized for regulatory T cell (Treg) recruitment and graft tolerance. Stellate cells (SCs) have various immunomodulatory functions: recruitment of Tregs and induction of T-cell apoptosis. Here, we designed a unique immune-privileged microenvironment around implantable islets through overexpression of CCL22 proteins by SCs. We prepared pseudoislets with insulin-secreting mouse insulinoma-6 (MIN6) cells and human SCs as a model to mimic naive islet morphology. Our results demonstrated that transduced SCs can secrete CCL22 and recruit Tregs toward the implantation site in vivo. This study is promising to provide a fundamental understanding of SC-islet interaction and ligand synthesis and transport from SCs at the graft site for ensuring local immune tolerance. Our results also establish a new paradigm for creating tolerable grafts for other chronic diseases such as diabetes, anemia, and central nervous system (CNS) diseases, and advance the science of graft tolerance. Keywords: Islet transplantation, Immune engineering, Regulatory T cells, Stellate cells, CCL22 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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