Regulatory Dendritic Cells Induced by Mesenchymal Stem Cells Ameliorate Dextran Sodium Sulfate-Induced Chronic Colitis in Mice

Abstract

Background/AimsRegulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice.MethodsImmature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice.ResultsAfter co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), was decreased, but that of CD11b, IL-10, and transforming growth factor-β (TGF-β) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-α, and IFN-γ decreased, but that of IL-10, TGF-β, and Foxp3 increased in the MSC- and MSC-DC-injected groups.ConclusionsOur data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

Sishen Pill Treatment of DSS-Induced Colitis via Regulating Interaction With Inflammatory Dendritic Cells and Gut Microbiota

“…Some studies indicated that adoptive transfer of bone marrow-derived DCs exacerbated DSS-induced colitis in mice, while selective genetic ablation of DCs attenuated the severity of colitis. This hinted that DCs are critical in pathogenetic process of DSS-induced colitis, and anti-DC therapy can effectively block inflammatory cells infiltration to the inflamed colon and inhibit inflammation to protect against DSS colitis (Berndt et al, 2007;Massafra et al, 2015;Jo et al, 2018). It has been shown that inflammatory DCs can induce Th1 and Th17 cell response, inhibit the T regulatory cell function, and lead to imbalance between pro-inflammatory and anti-inflammatory factors, as well as induce epithelial cell damage and colitis (Wang et al, 2018).…”

“…Some studies indicated that adoptive transfer of bone marrow-derived DCs exacerbated DSS-induced colitis in mice, while selective genetic ablation of DCs attenuated the severity of colitis. This hinted that DCs are critical in pathogenetic process of DSS-induced colitis, and anti-DC therapy can effectively block inflammatory cells infiltration to the inflamed colon and inhibit inflammation to protect against DSS colitis ( Berndt et al, 2007 ; Massafra et al, 2015 ; Jo et al, 2018 ).…”

Mesenchymal stem cells activate Notch signaling to induce regulatory dendritic cells in LPS-induced acute lung injury

“…Previous studies have shown that the maturity of classical dendritic cells (cDCs) in the lungs of ALI mice increased significantly, while inhibition of DCs maturation reduced the inflammatory response and pathological damage in the lungs [12,13]. MSC induced mature DCs (mDCs) differentiation into regulatory DC (DCreg) with low expression of CD80 and CD86 DCreg, which induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice [14]. MSC also abrogated the capacity of mDC migration to CCL19, or for DC to display MHC class II peptide complexes recognized by specific antibody, or ovalbumin-pulsed DC to support antigen-specific CD4 + T cell proliferation [15].…”

The Achievements and Challenges of Mesenchymal Stem Cell-Based Therapy in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

“…Administration of the MSC-DCs in DSS-induced colitis mice causes colon tissue IL-6, IFN-γ, and TNF-α to decrease while Foxp3, IL-10, and TGF-β increase. This implicates that MSCs differentiate DCs into regulatory DCs, which ameliorate colitis [23] and also suppress inflammatory phenotype of DCs in a galectin-3-dependent manner [24]. It is also documented that the regulatory DCs further trigger the production of Tregs to enhance the anti-inflammatory effect of MSCs in immune disorders.…”