Table 2.

Main functions of RNA modifications on various immune cells

Type of Immune cell	RNA modifications	Regulatory enzymes	Target RNA	Main functions	Ref.
T cells	m5C	NSUN2	IL17A	Enhances IL-17A mRNA translation.	306
(uncategorized)	m7G	RNMT	TOP	Modulates ribosome synthesis and activate T cells.	142
CD4+ T cells	m6A	ALKBH5	CXCL2, IFNG	Enhances the pathogenicity of CD4+ T cells.	315
(uncategorized)		METTL3	Cd40, Cd80, Tirap	Promotes DC function in CD4+ T-cell activation.	365
	m5C	NSUN1	HIV TAR RNA	Hamper HIV-1 transcriptional elongation and viral latency in CD4+ T cells.	317
		N.A.	N.A.	Associated with immune system, cytokine signaling and interferon signaling in SLE.	318
	ac4C	N.A.	USP18, GPX1, RGL1	Regulates mRNA catabolic processes and translational initiation in SLE.	319
	Uridylation	TUTases	N.A.	Reduces the stability of miRNAs and promotes CD4+ T cell activation.	226
	A-to-I editing	ADAT1	dsRNA	Participates in thymic T cell maturation	307,308
Th1/Th2 cells	m6A	N.A.	N.A.	Influences the Th1/Th2 imbalance in allergic asthma.	323
Th17 cells	m6A	METTL14	miR-149	Regulates Th17 differentiation in intestinal inflammation and malignancy.	327
Tfh cells	m6A	METTL3, METTL14	ICOS	Attenuates Tfh cell differentiation.	331
		METTL3	Tcf7	Activates Tfh transcriptional program to maintain Tfh differentiation.	332
Treg cells	m6A	METTL14	N.A.	Facilitates the differentiation of Treg and suppress the inflammatory response in IBD.	336
		N.A.	Socs	Maintains the functions and stability of Treg cells.	337
CD8+ T cells	m6A	N.A.	N.A.	Regulates CD8+ T cells infiltration in cancers.	342–344
		YTHDF1	mRNAs encoding lysosomal proteases	m6A modification in DCs suppresses the cross-priming of CD8+ T cells.	346
		METTL14, YTHDF2	Ebi3	m6A in macrophages maintains CD8+ T cell differentiation and activation.	423
		FTO	c-Jun, JunB, C/EBPβ	Restricts glycolytic metabolism of cancer cells to activate CD8+ T cells.	347
	m1A	N.A.	N.A.	Negatively related to CD8+ proliferation ability of T effector cells in colon cancer.	348
	m5C, Ψ	N.A.	N.A.	Influences immune responses of CD8+ T cells.	309
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.	355
		METTL3	lncRNAs	Promotes DNA recombination and development in B cells.	356
		FTO, YTHDF2	HSF1	Suppresses proliferation, migration, and invasion in plasma cells of multiple myeloma.	357
	A-to-I editing	ADAR1	N.A.	Critical for normal B lymphopoiesis in the bone marrow and peripheral maintenance.	358
DCs	m6A	N.A.	N.A.	Associated with the infiltration or depletion of DCs cancers and IBD.	363,364
		N.A.	lnc-Dpf3	Facilitates DC migration and inflammatory responses functions in a feedback manner.	447
		METTL3	Tirap, Cd40, Cd80	Activates DCs through TLR4/NF-κB signaling pathway and T-cell activation.	365
		YTHDF1	mRNAs encoding lysosomal proteases	Restricts cross-priming of CD8+ T cells mediated by DCs.	346
	m6A/Ψ	N.A.	N.A.	May influence the activations of DCs.	8
	A-to-I editing	ADAR1	N.A.	Essential for the differentiation, functionality, and survival of DCs.	366
NK cells	m6A	METTL3	Ptpn11	Maintains homeostasis and anti-tumor immunity of NK cells.	371
		YTHDF2	Tardb	Inhibits IL-15–mediated NK cell survival, proliferation, and effector functions.	372
Macrophages and/or monocytes	m6A	METTL14, YTHDF1	Socs1	Declines macrophage responses to acute bacterial infection.	387
		YTHDF2	MAP2K4, MAP4K4	Promotes LPS-induced inflammatory response in macrophages.	388
		METTL14, YTHDF2	Ebi3	Regulates macrophages-mediated CD8+ T cell differentiation and activation to inhibit tumor growth.	423
		N.A.	HIV-1 RNA	Facilitates HIV-1 escaping from innate antiviral immune responses of macrophages.	374
		METTL3	viral RNAs	Limits the innate sensing efficacy of macrophages for viral RNA.	379
		ALKBH5		Inhibits viral replication in macrophage.	380
		hnRNPA2B1	CGAS, IFI16, STING	Facilitates immune response to DNA viruses in macrophages.	434
		ALKBH5	antiviral transcripts	Increases interferon production and antiviral innate responses in macrophages.	382
		YTHDF3	FOXO3	Inhibits antiviral immunity under homeostatic conditions in macrophages.	381
		METTL3, YTHDF2	PGC-1α	Increases ROS accumulation and proinflammatory cytokines level in inflammatory monocytes.	384
		N.A.	N.A.	Negatively related to the immune response of monocytes in colorectal cancer.	385
		IGF2BP2	TSC1, PPAR-γ	Promotes M2 macrophages differentiation.	443
		METTL3	Irakm	Activate macrophages via TLR signaling.	386
		METTL3	MALAT	Promotes pyroptosis and inflammation of macrophages.	389
		N.A.	N.A.	Possibly promotes infiltration of macrophages in colorectal cancer.	395
	Uridylation	TUT7	Zc3h12a	Stabilize IL6 mRNA expression in TLR4-mediated inflammation in macrophages.	227
	A-to-I editing	ADAR1	N.A.	Promotes the differentiation, functionality, and survival of and alveolar macrophages.	366
		ADAR1	N.A.	Participates in trained immunity	383
		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.	390
Granulocytes	m6A	METTL3	c-Rel, RelA	Inhibit neutrophil infiltration in papillary thyroid cancer progression.	464
		N.A.	N.A.	Related to the infiltration of neutrophils in breast cancer and colorectal cancer.	393–395

m⁶A N⁶-methyladenosine, m⁵C 5-methylcytosine, m¹A N¹-methyladenosine, m⁷G 7-methylguanosine, ac⁴C N⁴-acetylcytidine, ψ pseudouridine, A-to-I editing adenosine-to-inosine RNA editing, DC dendritic cell, SLE systemic lupus erythematosus, IBD inflammatory bowel disease, ROS reactive oxygen species, TLR toll-like receptors, LPS Lipopolysaccharide, HIV human immunodeficiency virus, dsRNA double-stranded RNA