Neuropilin 1 and CD25 co-regulation during early murine thymic differentiation

Abstract

Neuropilin 1 (NP1) is a receptor for both semaphorin and vascular endothelial growth factor expressed by subpopulations of neuronal and endothelial cells. In the immune system, NP1 is present on dendritic and regulatory T cells. Here, we show that NP1 is expressed in the murine thymus, starting on day 12.5 of gestation. In the adult, NP1 is mainly expressed by CD4(-)CD8(-) double negative cells, CD4+CD8+ double positive cells, and CD4+CD25+ regulatory T cells but barely detected in single CD4+ and CD8+ positive thymocytes. Within the CD4(-)CD8(-)CD3(-) (triple-negative, TN) immature cells, NP1 expression starts in TN3 (CD44(-)CD25+) and increases in TN4 (CD44(-)CD25(-)) cells. In order to study the role of NP1 in thymocyte differentiation, we generated mice in which the np1 gene is selectively disrupted in the T-cell lineage. The mutant mice display normal thymocyte, peripheral, conventional and CD4+CD25+Foxp3+ regulatory T-cell populations. However, we observe a down-regulation of the CD25 expression between the TN3 and TN4 stages that is (i) correlated to increased expression of NP1 in control mice and (ii) altered in mutant mice, suggesting that NP1 is co-regulated with CD25 during early immature thymocyte differentiation.

Neuropilin-1 attenuates autoreactivity in experimental autoimmune encephalomyelitis

“…Several reports have shown that Nrp1 is important for T reg cell development (23,24), and Nrp1 has been proposed as a receptor for TGF-β (25). Whether this interaction actually contributes to signaling, the functional activity of T reg cells is enhanced by Nrp1:TGF-β ligation.…”

IL-17–producing invariant NKT cells in lymphoid organs are recent thymic emigrants identified by neuropilin-1 expression

“…We and others have reported Nrp-1 expression on activated human T cells 29,38 and immature proliferating murine thymocytes. 28,39 Therefore, Nrp-1 might be a general marker of TCR-and pre-TCR activation, and its presence on RTE iNKT cells, but not on naive and RTE conventional T cells, is likely because of the unconventional selection and development processes of iNKT cells, which require TCR-triggered proliferative expansion shortly before egress. Previous studies have shown that RTE iNKT cells share the thymic stage II phenotype (CD44 high NK1.1 Ϫ ).…”

“…[27][28][29] However, among immature cortical double-negative (DN) and DP thymocytes, Nrp-1 is highly expressed on stages corresponding to the ␤-selection and pre-TCR-mediated expansion phases. 28 Accordingly, in short-pulse BrdU experiments, we found that blastic proliferating (FSC high BrdU ϩ ) thymocytes all expressed high levels of Nrp-1 compared with smaller nonproliferating cells, which expressed low levels of Nrp-1 (supplemental Figure 1, available on the Blood Web site; see the Supplemental Materials link at the top of the online article). The iNKT cell lineage diverges from conventional ␣␤ T cells at the DP stage.…”

“…26 Nrp-1 is also expressed on immature thymocytes, but its function in these cells is less well characterized. 27,28 The expression of Nrp-1 in other murine T-cell subsets has not been investigated to date.…”

Advanced Glycation End Products Suppress Neuropilin-1 Expression in Podocytes by a Reduction in Sp1-Dependent Transcriptional Activity

“…Although NRP1 initially received its name from the neuronal localization, it is now known that NRP1 and other members of this family are expressed in a variety of tissue types [7,8,9,10,11]. Although NRP1 has been well studied in the neuronal and vascular systems, NRP1 expression in kidney podocytes has only recently received attention [7, 12].…”