Table 1.

The role of LILRB family in infectious, autoimmune and neurodegenerative diseases.

Diseases	LILRBs	Ligands	Expressing cells	Mechanisms	References
Viral infections
CMV	LILRB1	UL18	Cytotoxic T cell	Lysis of CMV-infected cells	238
		UL18	NK cell	Inhibit NK cytotoxic activity	236
		UL18	DC	Inhibit DC migration, maturation, and allogeneic T cell proliferation	145, 237
			Lymphocyte	CMV reactivation after lung transplantation	239
HIV-1	LILRB2		Monocyte	Impair monocyte antigen presentation	124
		HLA-B	Myelomonocytic cell	Induce myelomonocytic tolerogenesis	241
		HLA-I	DC	Dysregulation of cDCs	243
		HLA-G	Myeloid DC	Modulate DC antigen presentation and proinflammatory cytokine secretion	244
	LILRB1, LILRB3		Myeloid DC	NA	247
	LILRB1	S100A9	NK cell	Enhance NK cell anti-HIV-1 activity	85
DENV	LILRB1			Enhance DENV replication	86
				Overcome cell-autonomous immunity, boosting DENV intracellular survival	251
				Resistant to TLR/anti-IgM stimulation in CD19+CD27+ naïve B cells	252
SARS-CoV-2	LILRB4		MDSC	Elevated inflammation and regulatory B/T cell accumulation	255
EBV	LILRB1		CD8+ T cell	Inhibiting IFN-γ production to impair immunity	182, 257
CHB virus	LILRB1		NK cell	Reduce NK cell degranulation and IFN-γ production	258
Zika virus	LILRB1, LILRB2			Mutations impact in utero transmission chances	108
Reovirus	LILRB2/PirB			Essential for reovirus replication and neuropathogenicity	259
Bacterial infections
Mycobacterium tuberculosis	LILRB1		NK cell	Decrease CD107a and IFN-γ expression	260
	LILRB2		MDSC	Transition between immunosuppressive and proinflammatory states	261
	LILRB5		Cytotoxic T cell	Enhance cytotoxic T cell proliferation	263
Staphylococcus aureus	LILRB1, LILRB3/PirB		Macrophage	Influence TLR-mediated cytokine production	264
	LILRB3		Neutrophil	Regulate neutrophil activation and antimicrobial functions	169
Salmonella	LILRB2, LILRB4		Antigen presenting cell	Induce tolerogenic antigen-presenting cells	131
Escherichia coli	LILRB1, LILRB4, PirB		Macrophage	Enhanced proinflammatory cytokine production and MAPK/NF-kB activation	265
Parasite infections
Plasmodium falciparum	LILRB1	RIFIN	NK and B cells	Regulate IgM production and NK-mediated killing	63, 64
			B cell	Modulates inflammatory cytokine release	274
	LILRB2	RIFIN		Modulate immune response for immune evasion	66
Toxoplasma gondii	LILRB1	HLA-G	NK cell	NA	277
	LILRB4		MDSC	Alter ARG1 and IL-10 expression via SHP2/STAT6, leading to MDSC dysfunction	278
Trypanosoma cruzi	LILRB1		CD4+ T cell	Modulate parasite-specific T cell response	279
Autoimmune diseases
Autoimmune thyroid diseases	LILRB1		CD4+/CD8+ T cell	Disrupt IL-10 synthesis and cell proliferation	281
Rheumatoid arthritis	LILRB1	HLA-G	CD8+ T cell	Regulate CD8+ T cell activation	283
		Soluble HLA-G		Binding capacity dictates anti-inflammatory protection	284
Systemic lupus erythematosus	LILRB1		Peripheral blood B cell	Impaired LILRB1 expression and function	285
	LILRB4		Monocytoid DC	Loss-of-function polymorphisms affect inflammatory cytokine levels	106
	LILRB4		Plasmablast and plasma cell	Ectopically expressed	286
Multiple sclerosis	LILRB1	HLA-G		Modulate T-cell infiltration and immune-inflammatory response	287
	LILRB4			Influence Th1/Th17 proliferation and proinflammatory factor release	289
Neurodegenerative disease
Alzheimer's disease	LILRB2/PirB	Aβ oligomers		Causes synaptic toxicity and impaired developmental plasticity	291
	LILRB2	Aβ oligomers, L-α-phosphatidylserine	Microglia	Inhibits TREM2 signaling	292
	LILRB4	ApoE	Microglia	Dampening microglia phagocytosis of amyloid plaques	84

Aβ, β-amyloid; ApoE, apolipoprotein E; ARG, Arginase-1; CHB, chronic hepatitis B; CMV, cytomegalovirus; DC, dendritic cell; DENV, dengue virus; EBV, Epstein-Barr virus; HIV-1, human immunodeficiency virus type 1; HLA, human leukocyte antigen; IFN-α, interferon-alpha; IL-10, interleukin-10; MDSC, myeloid-derived suppressor cell; NK, natural killer; RIFINs, repetitive interspersed families of polypeptides; S100A9, S100 calcium binding protein A9; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TLR, toll-like receptor.