A neuronal receptor, neuropilin-1, is essential for the initiation of the primary immune response

Abstract

The initiation of a primary immune response requires contact between dendritic cells (DCs) and resting T cells. However, little is known about the proteins that mediate this initial contact. We show here that neuropilin-1, a receptor involved in axon guidance, was expressed by human DCs and resting T cells both in vitro and in vivo. The initial contact between DCs and resting T cells led to neuropilin-1 polarization on T cells. DCs and resting T cells specifically bound soluble neuropilin-1, and resting T cells formed clusters with neuropilin-1-transfected COS-7 cells in a neuropilin-1-dependent manner. Functionally, preincubation of DCs or resting T cells with blocking neuropilin-1 antibodies inhibited DC-induced proliferation of resting T cells. These data suggest that neuropilin-1 mediates interactions between DCs and T cells that are essential for initiation of the primary immune response and show parallels between the nervous and immune systems.

Neuropilin‐1 is not a marker of human Foxp3+ Treg

“…In the immune system, we and others have shown that Nrp-1 is involved in the priming of T cells by DC [7] and in the regulation of the immunological synapse and response [8,9]. More recently, Sarris et al have extended our findings by demonstrating that high expression of Nrp-1 on Treg cells promoted their prolonged interaction with immature DC [10].…”

The brain within the tumor: new roles for axon guidance molecules in cancers

“…Two examples are slit2 and Sema3A that in addition to their role in angiogenesis and neuronal development are very potent inhibitors of dendritic cell activation and of the immune response. 167,168 However, it is not because tumor cells express some axon guidance proteins that their function in these cells is identical and it would probably be a mistake to directly apply models based on neurons to tumor cell biology. For instance, the semaphorin receptors appear to be distinct in the immune system and nervous system.…”

Regulation of immune cell responses by semaphorins and their receptors

“…65 In addition, NP-1 is also a receptor for vascular endothelial growth factor (VEGF) in both endothelial cells (ECs) and tumor cells. 66 In the immune system, NP-1 is expressed in DCs and T cells, 67 where it negatively regulates immune responses. It is also noteworthy that NP-1 plays a key role in tumor angiogenesis through interactions with VEGF.…”

“…NP-1 has been shown to help initiate primary immune responses through homophilic interactions at the contact sites between T cells and DCs. 67 In addition, NP-1 was identified as a specific marker for CD4 1 CD25 1 regulatory T cells (Tregs). 69 Recently, one report suggested that NP-1 in Tregs contributes to prolong contact between Tregs and DCs, resulting in the inhibition of T-cell activation at steady state.…”