Acetylsalicylic acid (ASA) treatment enhances immunomodulatory properties of stem cells from exfoliated deciduous teeth (SHED). (A) ASA treatment significantly increased SHED-mediated T-cell apoptosis, as indicated by increased numbers of AnnexinV+7AAD– and AnnexinV+7AAD+ double-positive apoptotic T cells in an in vitro coculture system. (B) Th17 induction assay showed that ASA treatment significantly increased the capacity of SHED to downregulate the levels of Th17. (C) Schema showing SHED infusion in dextran sodium sulfate (DSS)–induced experimental colitis mice. (D) Colitis mice showed significantly reduced body weight from 5 to 10 d after DSS induction. Both SHED and ASA-SHED transplantation rescued body weight loss compared with the nontransplant group at 10 d post-DSS induction. However, ASA-SHED showed more significant rescue of body weight loss than did untreated SHED. (E) Disease activity index (DAI) was significantly increased in mice with colitis compared with the C57BL/6J control mice from 5 to 10 d post-DSS induction. Although both SHED and ASA-SHED infusion significantly reduced the DAI scores, ASA-SHED showed more capacity to reduce DAI scores than did untreated SHED. (F, G) Hematoxylin and eosin (H&E) staining showed the infiltration of inflammatory cells (blue arrows) in the colon, with destruction of the epithelial layer (yellow arrows) in mice with colitis. ASA-SHED transplantation produced more significant rescue of disease phenotypes in the colon and reduction of histologic activity index (HAI) compared with the untreated control SHED group. (H, I) The levels of Th1 and Th17 were significantly elevated in colitis mice compared with C57BL/6J control mice at 10 d post-DSS induction. Compared with untreated SHED, ASA-SHED infusion resulted in significantly reduced levels of Th1 and Th17 cells in colitis mice at 10 d post-DSS induction. (J) The levels of Tregs were significantly reduced in mice with colitis compared with C57BL/6J control mice at 10 d post-DSS induction. ASA-SHED infusion exhibited a greater ability to upregulate Tregs levels in mice with colitis than did untreated SHED. (K–M) The levels of tumor necrosis factor–α (TNF-α), interleukin (IL)–6, and IL-17 in serum were markedly increased in colitis mice compared with C57BL/6J control mice at 10 d post-DSS induction, and ASA-SHED infusion significantly downregulated serum levels of TNF-α, IL-6, and IL-17. n = 5 in each group. Scale bar = 200 µm. *P < 0.05. **P < 0.01. ***P < 0.005. Error bars: mean ± SD.