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This study aimed to investigate the therapeutic effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on experimental autoimmune thyroiditis (EAT) and the underlying mechanisms by utilizing a porcine thyroglobulin-induced EAT rat model. The rats received four tail vein injections of vehicle or hUCMSCs at an interval of 7 days and were sacrificed on day 28 after the first injection. Hematoxylin and eosin staining and enzyme-linked immunosorbent assays (ELISAs) were used to assess the therapeutic effects of hUCMSCs on EAT. Splenic lymphocytes were isolated from rats, and the proportions of CD4 + T cell subsets were analyzed by flow cytometry. Splenic CD4 + T cells from EAT rats were cocultured with hUCMSCs. A loss-of-function assay for protein tyrosine phosphatase non-receptor type 2 (PTPN2) was performed to explore the involvement of PTPN2/signal transducer and activator of transcription 3 (STAT3) signaling on the therapeutic benefit of hUCMSCs in EAT. hUCMSC treatment significantly alleviated inflammation, reduced serum thyroid antibody levels, and decreased the ratios of IL-17α + /CD25 + FOXP3 + cells and serum IFN-γ/IL-4 in EAT rats. Furthermore, hUCMSC treatment upregulated PTPN2 protein expression in splenic lymphocytes of EAT rats as well as enhanced the PTPN2 protein level and attenuated phosphorylation of STAT3 in CD4 + T cells in vitro. Importantly, knockdown of Ptpn2 significantly reversed hUCMSC-mediated suppression of cell proliferation and hUCMSC-induced alterations in the expression of inflammatory cytokines in CD4 + T cells. Thus, hUCMSC treatment alleviates thyroid inflammation and the CD4 + T cell imbalance in EAT via PTPN2/STAT3 signaling, serving as a promising therapeutic approach for autoimmune thyroiditis.

endocrine journal

Human umbilical cord mesenchymal stem cells alleviate the imbalance of CD4&lt;sup&gt;+&lt;/sup&gt; T cells &lt;i&gt;via&lt;/i&gt; protein tyrosine phosphatase non-receptor type 2/signal transducer and activator of transcription 3 signaling in ameliorating experimental autoimmune thyroiditis in rats