Neuropilin-1 (Nrp-1) was recently identified as a possible surface marker for naturally occurring CD4+CD25+ regulatory T cells and is constitutively expressed on the cell irrespective of its activation status. Nrp-1 is a type 1 membrane protein with three unique functions. In neuronal cells, Nrp-1 binds the class 3 semaphorins, which are neuronal chemorepellents, and plays a role in the directional guidance of axons. It also form complexes with the plexinA subfamily members and mediate the semaphorin-elicited inhibitory signals into neurons. Moreover in endothelial cells, Nrp-1 binds a potent endothelial cell mitogen, vascular endothelial growth factor (VEGF)165 and thus regulates vessel formation (1). The protein is also described to mediate homophilic interactions between dendritic cells and T cells in human, which confirms its role in immune function. Amongst T cells, Nrp-1 is preferentially expressed on T regulatory cells (Tregs) (2). It has been suggested that Neuropilin-1 acts as glue between Tregs and dendritic Cells (4). Neuropilin-1 expression on Tregs has been shown to enhance their interactions with immature dendritic cells (iDCs) during antigen recognition (4).

Treg cells are potential components of the immune system controlling immune responsiveness to self and alloantigens. Apart from the expression of the two surface molecules, CD4 and CD25, Treg cells are also known to express the transcription factor Foxp3, which is essential for the development and function of Treg cells. Recently, several cell surface molecules, such as, CTLA-4, GITR, LAG3, GPR83, Folate receptor 4 have been shown to be expressed at high level on regulatory T cells. Besides the currently known other cell surface receptors for Treg cells such as the B7-family members PD1, and ICOS, are also up regulated in activated non-regulatory CD4+T cells.

Recent research works to identify a specific cell surface marker for Tregs has led to identification of Nrp-1 as a cell surface molecule that is expressed by 80% of CD4+CD25+ Tregs but not on naïve cells. Further studies reveal the expression of the Nrp-1 gene to be regulated by the transcription factor Foxp3. Ectotopic expression of FoxP3 in CD4+ T cells lead to up regulation of Nrp-1 and increases interaction time between Tregs and iDCs, resulting in higher sensitivity to limiting amounts of antigens (5). Anti-Nrp-1 antibody treatment interferes with interactions between Tregs and iDCs. Moreover the expression of the protein is also significantly low in naive non-regulatory T cells (CD4+CD25- T cells) and is further down regulated after TCR stimulation. Thus Nrp-1 represents a novel surface marker on Treg cells with several important functions.

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