Sca1⁺Lin⁻CD117⁻ Mouse Bone Marrow-Derived Mesenchymal Stem Cells Regulate Immature Dendritic Cell Maturation by Inhibiting TLR4-IRF8 Signaling Via the Notch-RBP-J Pathway

Abstract

Mesenchymal stem cells (MSCs) have a superior immunomodulatory capacity compared to other cells of the immune system, and they hold great promise for treating various immune disorders. However, their regulatory effects on the maturation of immature dendritic cells (imDCs) are not fully understood. In this study, we show that Sca-1LinCD117MSCs restrain the lipopolysaccharide-stimulated maturation transition of imDCs cocultured without exogenous cytokines. The Notch signaling pathway plays a critical role in the process by controlling interferon regulatory factor 8 (IRF8) expression in an RBP-J-dependent manner. We observed a high degree of H3K27me3 modification mediated by SUZ12 and a relatively low degree of H3K4me3 modification regulated by WDR5 at the IRF8 promoter during coculture. These data reveal a possible mechanism by which Sca-1LinCD117MSCs modulate imDC maturation and further support the role of MSCs in treating immune disorders.

Simulated microgravity increases CD226+Lin−CD117−Sca1+ mesenchymal stem cells in mice

“…HSCs and MSCs were identified based on their expression of Lin, Sca‐1, and CD117. HSCs were Lin − CD117 + Sca‐1 + and MSCs were Lin − CD117 − Sca‐1 + (Liu et al., 2015 , 2018 ; Purton & Scadden, 2007 ). All antibodies were purchased from Biolegend (San Diego, CA) and details are listed in Table S1 .…”

Intracellular HSP70L1 inhibits human dendritic cell maturation by promoting suppressive H3K27me3 and H2AK119Ub1 histone modifications

“…[19][20][21][22][23][24] Recent evidence has also demonstrated that these active and repressive histone modifications have both stage-specific effects on the promoter regions of transcription factors that direct DC subset commitment during differentiation and stimulus-dependent effects on the promoters of the genes that encode inflammatory signal molecules or phenotypes in DCs. [25][26][27][28] Thus, the identification of intrinsic regulators of the histone modifications required for the differentiation or maturation of specific DC subsets is critical for a complete understanding of DCassociated inflammatory responses and homeostasis. MoDCs are superior to the other three DC subsets in mediating inflammation and the artificial manipulation of DC-based immunotherapy because of their precursor number: monocytes represent 10-20% of peripheral blood mononuclear cells.…”