Table 1.

Summary of different types of semaphorins and neurotrophins, along with their receptors, actions and presence in immune cells.

Molecules	Types	Receptors on neural cells	Activities	Expression on immune cells
Semaphorins	Class 1 and 2 in invertebrates; class 3, 4, 5, 6, and 7 in vertebrates; class 8 in viruses Subclasses designated with letters (i.e., Sema3A or Sema4D, etc.) Class 1 and 4–7 semaphorins are transmembrane proteins; class 2, 3 and viral semaphorins are soluble proteins Sema4D has a soluble form	Plexins: grouped into four classes (A–D), and presenting many different subtypes Neuropilins: co-receptors for class 3 semaphorins	Axon guidance molecules with capacity to attract or repel axonal growth cones Modulation of synaptic activity in the hippocampus Plasticity in uterine sympathetic nerves Modulation of hormone release in the pituitary Organogenesis, angiogenesis, neuronal apoptosis and tumor progression Many immune functions: cell-to-cell contact, modulation of immunological synapses, regulation of immune cell activation (by serving as costimulatory molecules), proliferation, differentiation, cell migration, and cytokine production	4A Semaphorin: expressed on antigen-presenting cells (52) 4C Semaphorin: upregulated on follicular T helper cells (53) 4D Semaphorin: expressed on T cells, B cells and dendritic cells (DCs), markedly increased upon activation [reviewed in (49–51)] 6D Semaphorin: present in T cells, B cells and NK cells (49–51) 7D Semaphorin: seen in activated T cells and in double positive thymocytes (49–51) 3A Semaphorin: produced by activated CD4+ and CD8+ T cells, human blood peripheral monocytes, macrophages and DCs (54, 55) 3F Semaphorin: present in T-cell precursors in the human thymus (56)
Neurotrophins (all of them are soluble proteins)	Nerve growth factor (NGF) Brain derived neurotrophin factor (BDNF) Neurotrophin 3 (NT-3) Neurotrophin 4 (NT-4) Pro-forms and mature forms are released. Pro-forms can be cleaved intra or extracellularly	Tropomyosin-related kinase (Trk) receptors A, B and C, high-affinity receptors for mature forms of neurotrophins p75 neurotrophin receptor (p75NTR), “low-affinity receptor,” showing high affinity for pro-forms p75NTR is specifically re-expressed under cytokine influence and during injury [reviewed in (96–104)]	Mature forms promote cell survival, axonal and dendritic outgrowth, mainly via Trk receptors Neurotrophins (mainly their pro-forms) can also mediate axonal degeneration or apoptosis via p75NTR, when Trk receptors activation is reduced or absent Synaptic plasticity within the hippocampus Plasticity in uterine sympathetic nerves Immune functions: modulation of immune cells apoptosis, proliferation and cytokine production	BDNF: in vitro on activated human T cells, B cells and monocytes (82) NT-3, BDNF, TrkB, and TrkC: human immune cells (83) NGF, BDNF, NT-3, and NT-4/5: rat T cells, significantly increased upon antigen activation (84) BDNF, pro-BDNF, and Trk receptors: human B cells (92) TrkA: human monocytes (95) p75NTR: murine and human plasmacytoid dendritic cells (94) p75NTR and pro-BDNF: murine innate immune cells (93) Elevated levels of neurotrophins found in many different inflammatory scenarios (85–91)

These molecules are widely expressed in many different cell types, in some cases under the influence of cytokines in an inflammatory milieu.