CD126^hi umbilical cord mesenchymal stem cells sensitive to IL-6 ameliorate inflammatory bowel disease by producing...

Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation.

We assessed the regulatory effects of CD126 high (CD126^hi) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126^hi was evaluated by Hematoxylin and Eosin (H&E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student's t-test or one-way analysis of variance (ANOVA) with Tukey test.

The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126^hi HUMSCs but not in DSS-treated mice administered with CD126 low (CD126^lo) HUMSCs. Intriguingly, CD126^hi HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126^hi HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126^lo HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126^hi HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis.

Our results revealed a mechanism wherein CD126^hi HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126^hi HUMSCs for inflammatory diseases such as inflammatory bowel disease.