Table 2 Main functions of RNA modifications on various immune cells
From: RNA modifications: importance in immune cell biology and related diseases
Type of Immune cell | RNA modifications | Regulatory enzymes | Target RNA | Main functions | Ref. |
|---|---|---|---|---|---|
T cells | m5C | NSUN2 | IL17A | Enhances IL-17A mRNA translation. | |
(uncategorized) | m7G | RNMT | TOP | Modulates ribosome synthesis and activate T cells. | |
CD4+ T cells | m6A | ALKBH5 | CXCL2, IFNG | Enhances the pathogenicity of CD4+ T cells. | |
(uncategorized) | METTL3 | Cd40, Cd80, Tirap | Promotes DC function in CD4+ T-cell activation. | ||
m5C | NSUN1 | HIV TAR RNA | Hamper HIV-1 transcriptional elongation and viral latency in CD4+ T cells. | ||
N.A. | N.A. | Associated with immune system, cytokine signaling and interferon signaling in SLE. | |||
ac4C | N.A. | USP18, GPX1, RGL1 | Regulates mRNA catabolic processes and translational initiation in SLE. | ||
Uridylation | TUTases | N.A. | Reduces the stability of miRNAs and promotes CD4+ T cell activation. | ||
A-to-I editing | ADAT1 | dsRNA | Participates in thymic T cell maturation | ||
Th1/Th2 cells | m6A | N.A. | N.A. | Influences the Th1/Th2 imbalance in allergic asthma. | |
Th17 cells | m6A | METTL14 | miR-149 | Regulates Th17 differentiation in intestinal inflammation and malignancy. | |
Tfh cells | m6A | METTL3, METTL14 | ICOS | Attenuates Tfh cell differentiation. | |
METTL3 | Tcf7 | Activates Tfh transcriptional program to maintain Tfh differentiation. | |||
Treg cells | m6A | METTL14 | N.A. | Facilitates the differentiation of Treg and suppress the inflammatory response in IBD. | |
N.A. | Socs | Maintains the functions and stability of Treg cells. | |||
CD8+ T cells | m6A | N.A. | N.A. | Regulates CD8+ T cells infiltration in cancers. | |
YTHDF1 | mRNAs encoding lysosomal proteases | m6A modification in DCs suppresses the cross-priming of CD8+ T cells. | |||
METTL14, YTHDF2 | Ebi3 | m6A in macrophages maintains CD8+ T cell differentiation and activation. | |||
FTO | c-Jun, JunB, C/EBPβ | Restricts glycolytic metabolism of cancer cells to activate CD8+ T cells. | |||
m1A | N.A. | N.A. | Negatively related to CD8+ proliferation ability of T effector cells in colon cancer. | ||
m5C, Ψ | N.A. | N.A. | Influences immune responses of CD8+ T cells. | ||
B cells | m6A | METTL14 | N.A. | Mediates IL-7-induced cell proliferation of pro-B cell and large-pre-B-to-small-pre-B transition. | |
METTL3 | lncRNAs | Promotes DNA recombination and development in B cells. | |||
FTO, YTHDF2 | HSF1 | Suppresses proliferation, migration, and invasion in plasma cells of multiple myeloma. | |||
A-to-I editing | ADAR1 | N.A. | Critical for normal B lymphopoiesis in the bone marrow and peripheral maintenance. | ||
DCs | m6A | N.A. | N.A. | Associated with the infiltration or depletion of DCs cancers and IBD. | |
N.A. | lnc-Dpf3 | Facilitates DC migration and inflammatory responses functions in a feedback manner. | |||
METTL3 | Tirap, Cd40, Cd80 | Activates DCs through TLR4/NF-κB signaling pathway and T-cell activation. | |||
YTHDF1 | mRNAs encoding lysosomal proteases | Restricts cross-priming of CD8+ T cells mediated by DCs. | |||
m6A/Ψ | N.A. | N.A. | May influence the activations of DCs. | ||
A-to-I editing | ADAR1 | N.A. | Essential for the differentiation, functionality, and survival of DCs. | ||
NK cells | m6A | METTL3 | Ptpn11 | Maintains homeostasis and anti-tumor immunity of NK cells. | |
YTHDF2 | Tardb | Inhibits IL-15–mediated NK cell survival, proliferation, and effector functions. | |||
Macrophages and/or monocytes | m6A | METTL14, YTHDF1 | Socs1 | Declines macrophage responses to acute bacterial infection. | |
YTHDF2 | MAP2K4, MAP4K4 | Promotes LPS-induced inflammatory response in macrophages. | |||
METTL14, YTHDF2 | Ebi3 | Regulates macrophages-mediated CD8+ T cell differentiation and activation to inhibit tumor growth. | |||
N.A. | HIV-1 RNA | Facilitates HIV-1 escaping from innate antiviral immune responses of macrophages. | |||
METTL3 | viral RNAs | Limits the innate sensing efficacy of macrophages for viral RNA. | |||
ALKBH5 | Inhibits viral replication in macrophage. | ||||
hnRNPA2B1 | CGAS, IFI16, STING | Facilitates immune response to DNA viruses in macrophages. | |||
ALKBH5 | antiviral transcripts | Increases interferon production and antiviral innate responses in macrophages. | |||
YTHDF3 | FOXO3 | Inhibits antiviral immunity under homeostatic conditions in macrophages. | |||
METTL3, YTHDF2 | PGC-1α | Increases ROS accumulation and proinflammatory cytokines level in inflammatory monocytes. | |||
N.A. | N.A. | Negatively related to the immune response of monocytes in colorectal cancer. | |||
IGF2BP2 | TSC1, PPAR-γ | Promotes M2 macrophages differentiation. | |||
METTL3 | Irakm | Activate macrophages via TLR signaling. | |||
METTL3 | MALAT | Promotes pyroptosis and inflammation of macrophages. | |||
N.A. | N.A. | Possibly promotes infiltration of macrophages in colorectal cancer. | |||
Uridylation | TUT7 | Zc3h12a | Stabilize IL6 mRNA expression in TLR4-mediated inflammation in macrophages. | ||
A-to-I editing | ADAR1 | N.A. | Promotes the differentiation, functionality, and survival of and alveolar macrophages. | ||
ADAR1 | N.A. | Participates in trained immunity | |||
ADAR1 | miR-21 precursor | Reduces the generation of mature miR-21, therefore facilitating the polarization of macrophages toward the M2 phenotype via Foxo1-IL-10 axis. | |||
Granulocytes | m6A | METTL3 | c-Rel, RelA | Inhibit neutrophil infiltration in papillary thyroid cancer progression. | |
N.A. | N.A. | Related to the infiltration of neutrophils in breast cancer and colorectal cancer. |
