2. Academic Validation
  3. Exosomal miR-181d-5p Derived from Rapamycin-Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6

Exosomal miR-181d-5p Derived from Rapamycin-Conditioned MDSC Alleviated Allograft Rejection by Targeting KLF6

  • Adv Sci (Weinh). 2023 Oct 23:e2304922. doi: 10.1002/advs.202304922.
Chao Wei 1,  Yaru Sun 1,  Fanxing Zeng 1,  Xiunian Chen 1,  Li Ma 1,  Xiaoxue Liu 1,  Xiaolin Qi 1 2 3,  Weiyun Shi 1 2 3,  Hua Gao 1 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Eye Institute of Shandong First Medical University, Qingdao, 266071, China.
  • 2 Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan, 250117, China.
  • 3 School of Ophthalmology, Shandong First Medical University & Shandong Academy of Medical Science, Jinan, 250117, China.
PMID: 37870185 DOI: 10.1002/advs.202304922
Abstract

Immune rejection and side effects of long-term administration of immunosuppressants are the two major obstacles to allograft acceptance and tolerance. The immunosuppressive extracellular vesicles (EVs)-based approach has been proven to be effective in treating autoimmune/inflammatory disorders. Herein, the anti-rejection advantage of exosomes (Rapa-Exo) from rapamycin-conditioned myeloid-derived suppressor cells (MDSCs) over exosomes (Exo-Nor) from the untreated MDSCs is shown. The exosomal small RNA sequencing and loss-of-function assays reveal that the anti-rejection effect of Rapa-Exo functionally relies on miR-181d-5p. Through target prediction and double-luciferase reporter assay, Kruppel-like factor (KLF) 6 is identified as a direct target of miR-181d-5p. Finally, KLF6 knockdown markedly resolves inflammation and prolongs the survival of corneal allografts. Taken together, these findings support that Rapa-Exo executes an anti-rejection effect, highlighting the immunosuppressive EVs-based treatment as a promising approach in organ transplantation.

Keywords

KLF6; allograft rejection; exosome; miR-181d-5p; myeloid-derived suppressor cells.

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