Table 1.

Expression and functions NRPs in the immune system and related diseases.

NRPs	Expression		Functions	Related diseases	Reference
	Immune cells	Cellular context
NRP1	Dendritic cells (DCs) Plasmacytoid DC		Role in production of IFN-α (?) and viral clearance (?) Increases susceptibility to HTLV-1 virus Migration and induction of immunosuppression in TIDCs, correlation with disease progression (?)	Viral infection Retroviral infection Cancer	(82) (88) (106)
	myeloid DC (mDC)		Formation of immunological synapse (IS) with T cells by homophilic interaction between NRP1 on DC and T cells Induction of immune tolerance and prevent aberrant activation of T cells Reorganization of actin cytoskeleton and transmigration of DC to lymph node through Sema3A/NRP1/PlexinA1 axis Increases susceptibility toward HTLV-1 virus		(50) (50, 69, 77) (84) (87–89, 91, 92)
	Macrophages, microglia		Developmental vascularization Promotion of M2 type polarization, phagocytosis, induction of Tregs, and immunosuppression Migration to the hypoxic core of solid tumors through Sema3A/NRP1/PlexinA1/PlexinA4 axis Protumorigenic activities of TAMs Negative regulation of TAM proliferation in certain tumors through Sema3A binding (?)	EAE Cancer Cancer Cancer	(44, 123–125) (147, 148) (133, 134) (133, 134, 136, 137, 139) (135)
	Osteoclasts Osteoblasts		Osteoprotection by preventing osteoclastogenesis and promoting formation of osteoblasts		(156)
	T cells Thymocytes (premature)		Adhesion and deadhesion to thymic epithelial cells Actin reorganization (?) Egress from thymus (?)		(51, 179)
	Treg		Immunosuppression and induction of tolerance Migration of Treg to the tumor microenvironment Stability and function of Tregs	EAE GVHD Cancer	(181, 186–191, 200) (209) (218)
	CD8+ effector and memory cells	Viral infection Priming by liver sinusoidal endothelial cells	Not known Not known		(231) (233)
	Mucosal CD8+Foxp3+ cells Tumor-infiltrating CD8+ cells	Exposure to gut specific antigen	Suppressed CD4+ T cell proliferation in vitro Not known	Metastatic melanoma	(232) (234)
	NKT, recent thymic emigrant IL-17-producing iNKT cells		Role in development (?) Egress from thymus (?) Interaction between iNKT and macrophages (?)		(57, 58)
	Tfh		B cell differentiation Migration to and retention of Tfh in secondary germinal center of lymphoid organs	Angioimmunoblastic T cell lymphoma (AITL)	(56)
	Basophils		Not known		(264–266)
	Mast cells		Not known		(264–266)
NRP2	DCs mDCs		Interaction with T cells Chemokine guided migration		(33) (34, 110)
	Macrophages/microglia Alveolar, bronchial, and intravascular macrophages		Not known		(136)
	Microglia	LPS challenge	Negative feedback regulation of proinflammatory responses		(154, 155)
	Peritoneum macrophage		Phagocytosis (?)		(153)
	TAMs		Not known		(136, 151)
	Osteoclasts/osteoblasts		Negative regulation of osteoclast number Promotion of osteoblast formation	Osteosarcoma	(48, 161–163)
	T cells CD4+CD8+ developing thymocytes		Migration Differentiation (?)		(249)
	VY9Vδ2 T cells		Not known	T-ALL T-LBL Non-Hodgkin’s lymphoma	(260)
	CD4+ effector T cells		Negative regulation of proliferation Immunomodulation in graft transplant	GVHD	Published abstract, ATC, 2015
	CD4+Foxp3+ Treg		Negative regulation of proliferation Immunomodulation in graft transplant	GVHD	Published abstract, ATC, 2015
	Basophils		Not known		(264–266)
	Mast cells		Not known		(264–266)

NRPs, neuropilins; NRP1, neuropilin-1; NRP2, neuropilin-2; Sema3A, Semaphorin 3A; Tfh, T follicular helper; HTLV, human T-cell leukemia virus; TIDCs, tumor-infiltrating DCs; TAM, tumor-associated macrophage; EAE, experimental autoimmune encephalomyelitis; NKT, natural killer T; T-ALL, T-cell acute lymphoblastic leukemia; T-LBL, T-cell lymphoblastic lymphoma; iNKT, invariant natural killer T; GVHD, graft-versus-host disease; T_reg, regulatory T cell.