CD4+Foxp3+T Regulatory Cells Promote Transplantation Tolerance by Modulating Effector CD4+ T Cells in a Neuropilin-1-Dependent Manner

Discussion Regulatory T cell malfunction has been widely associated with increased inflammatory immune responses. Understanding Treg cells biological processes and mechanisms of suppression are pivotal for recognizing new targets for therapy. Nrp1 has been previously proposed as a cell marker for thymic-derived Treg cells (39); but its expression has also been described on T cells during allogeneic skin graft rejection (22), sepsis (40), IL-10 deficiency (41), and anti-tumor immune responses (42, 43). Moreover, Nrp1 deficiency on Foxp3+ Treg cells has been associated with lack of immune suppression, predominantly affecting tumor growth (14, 15, 44) and worsening EAE severity (45). In this work, we focused on analyzing the role of Nrp1 specifically on Treg cells during the induction of skin transplant tolerance. In one of our previous studies we demonstrated that Nrp1+ Treg cells drive transplantation tolerance, proposing the modulation of conventional CD4+ T cell phenotype as a possible mechanism (22). To get more insight regarding this observation, we obtained conditional knockout animals in which the lack of Nrp1 expression is restricted to Foxp3+ Treg cells (24). First, we extensively analyzed the phenotype of T cells in these genetically modified mice, including Foxp3+ Treg cells, finding no aberrant expression of Treg cell-associated markers in animals containing Nrp1KO Treg cells compared to controls (Figures 1, 2). Next, we designed in vitro experi...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research