Dendritic cells with METTL3 gene knockdown exhibit immature properties and prolong allograft survival

N6‐methyladenosine RNA methylation: A novel regulator of the development and function of immune cells

“…Knockout of Mettl3 in DCs downregulates expression of the costimulatory molecules CD86, CD80, and CD40 and reduces secretion of the functional cytokines IL-6, TNF-α, and IL-12 under LPS stimulation (H. Wang et al, 2019). Some consequences were verified in other results of Ruan's research team (H. Wu et al, 2020a). Further, Mettl3-silenced DCs express lower levels of major histocompatibility complex (MHC)-II and lower levels of secreted IFNγ (H. Wu et al, 2020a).…”

“…METTL3 regulates the T H 1/T H 2 ratio (Figure 3). Mettl3 silencing in DCs causes a shift in T cell subsets and function from T H 1 to T H 2 cells (H. Wu et al, 2020a). DCs play an important role in regulating immune tolerance after allogeneic organ transplantation.…”

“…T H 1 cells are associated with immune rejection, and T H 2 cells are associated with immune tolerance. Mettl3 ‐silenced DCs possess immature properties and help to prolong allograft survival in murine heart transplant recipients (H. Wu et al, 2020a). Exosomes derived from donor DCs (Dex) participate in immune rejection after organ transplantation.…”

The Emerging Clinical Application of m6A RNA Modification in Inflammatory Bowel Disease and Its Associated Colorectal Cancer

“…However, the specific loss of METTL3 in DCs leads to impaired phenotype and functional maturation of DCs, decreased expression of co-stimulatory molecules CD40, CD80, and cytokine interleukin (IL)-12, which reduces its ability to stimulate T cell response in vivo and in vitro. Similarly, Wu et al found that METTL3-silences of DCs showed immature characteristics and prolonged allograft survival after constructing a mouse heart transplant model with METTL3 knockout, 65 highlighting the regulatory role of m6A in DCs maturation and host immune response. Also, one study showed that C-C chemokine receptor 7 (CCR7) stimulation up-regulates lnc-Dpf3 by removing the m6A modification to prevent RNA degradation.…”

Targeting the RNA m6A modification for cancer immunotherapy

“…The underlying mechanism was the enhancement of the translation efficiency of CD40, CD80, and Toll/interleukin-1 receptor (TIR) domain-containing adaptor protein (TIRAP) by METTL3, leading to the secretion of proinflammatory cytokines [ 46 ]. METTL3-silenced DCs have reduced expression levels of MHC-II, costimulatory molecules (CD80, CD86), and inflammatory cytokines (IFN-γ, IL-12), thereby inducing immune tolerance and prolonging allograft survival in mouse heart transplantation [ 47 ]. This suggests that METTL3 helps maintain the mature properties of DCs.…”