Adipose-Derived Mesenchymal Stem Cells Reduce Lymphocytic Infiltration in a Rabbit Model of Induced Autoimmune Dacryoadenitis

PURPOSE: To investigate the immunoregulatory roles of adipose-derived mesenchymal stem cells (ADSCs) in autoimmune dacryoadenitis. METHODS: Rabbits were treated with ADSCs or phosphate-buffered solution on days 1, 3, 5, 7, and 9 after injection of activated peripheral blood lymphocytes, and clinical scores were determined by assessing tear production, break-up time, and fluorescein and hematoxylin and eosin staining. Inflammatory response was determined by measuring the expression of different mediators of inflammation in the lacrimal glands. The Th1/Th17-mediated autoreactive responses were evaluated by determining the proliferative response and the expression of cytokine genes and the lineage-determining transcription factors. The frequency of regulatory T cells (Tregs) was also examined. RESULTS: The ADSC-treated rabbits showed decreased autoimmune responses, and the secretory function of their lacrimal gland was restored significantly. Treatment with ADSCs downregulated the Th1 and Th17 responses but enhanced Tregs function. In addition, ADSC treatment noticeably suppressed the expression of matrix metalloproteinase (MMP)-9, MPP-2, IL-1β, and IL-6, whereas it enhanced the expression of the anti-inflammatory cytokine IL-10. CONCLUSIONS: Our results demonstrated that ADSC administration efficiently ameliorates autoimmune dacryoadenitis mainly via modulating Th1/Th17 responses.