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Published on: June 7, 2017
Enhanced Therapeutic Effect of IL-10-ADSCs on Rabbit Autoimmune Dacryoadenitis By Suppressing T Follicular Helper
Lu Zhao1, Na Li1, Xinrui Shi1
1Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin Medical University, Tianjin, China.
Purpose:
Mesenchymal stem cells (MSCs) represent a promising therapeutic strategy in clinical research for dry eye, and their immunomodulatory effects can be enhanced through genetic modification. In this study, we constructed interleukin-10 (IL-10) gene-modified adipose-derived MSCs (IL-10-ADSCs) and investigated their protective effects and underlying mechanisms on rabbit autoimmune dacryoadenitis, an animal model of autoimmune dry eye.
Methods:
ADSCs were isolated from rabbit adipose tissue and transduced with IL-10 overexpressing lentivirus. Then the preventive and therapeutic effects of IL-10-ADSCs on rabbit autoimmune dacryoadenitis were evaluated. Flow cytometry and Western blot were performed to assess the immunomodulatory effects of IL-10-ADSCs on T follicular helper (Tfh) cells. Bioinformatic analyses and functional gain and loss assays were used to determine the molecular mechanism underlying the effects of IL-10-ADSCs on Tfh responses.
Results:
We demonstrated that IL-10-ADSCs maintain the cell surface phenotype and multi-differentiation potentials of MSCs. Intravenous injection of IL-10-ADSCs markedly attenuated autoimmune dacryoadenitis, yielding significantly superior clinical and pathological improvements compared to ADSCs. Further investigation revealed that IL-10-ADSCs administration significantly suppressed Tfh cell responses in vivo and in vitro, contributing to reduced inflammation and improved tissue damage. Mechanistically, IL-10-ADSCs exert their suppressive function on Tfh cells partially through the miR-142-5p/RC3H1 axis. Notably, IL-10-ADSCs subconjunctivally administered after disease onset efficiently ameliorated the severity of autoimmune dacryoadenitis.
Conclusions:
IL-10-ADSCs ameliorate autoimmune dacryoadenitis by suppressing Tfh cell responses via suppressing the miR-142-5p/RC3H1 axis. The enhanced therapeutic effects of IL-10-ADSCs could be of significant value in improving the effectiveness of stem cell therapy in autoimmune dry eye.
