Podoplanin negatively regulates CD4+ effector T cell responses

Podoplanin is a negative regulator of Th17 inflammation

“…Human PDPN + CD4 + cells also have an mRNA signature demonstrating higher levels of genes associated with nonpathogenic Th17 cells, including IL10, IL9, Ikzf3, Ahr, and IL1rn, and several of these genes are involved in the regulation of IL-10 (7). It has been suggested that a decreased ability of T cells to respond to IL-7 through decreased levels of IL7R may contribute to its role as a negative regulator by affecting the maintenance and survival of T effector cells (38), consistent with the lower expression of IL7R we observed on human PDPN + CD4 + cells. Given that the gene signatures of pathogenic and nonpathogenic Th17 cells have been previously described in murine EAE with a clear division in the types of genes expressed in each of the mRNA profiles, it is notable that the mRNA profile of PDPN + CD4 + T cells more closely resembles the profile of nonpathogenic Th17 cells in murine EAE.…”

“…A mouse model with a CD4 + T cell-specific gene silencing of Pdpn demonstrated that these mice experienced spontaneous EAE with a more severe course, as well as a greater accumulation of CD4 + T cells within the CNS. Additionally, a transgenic mouse model that expressed Pdpn driven by the CD2 promoter exhibited severe peripheral lymphopenia, defects in IL-7-mediated T cell expansion and survival, reduced CD4 + T cell burden in the CNS, and more rapid recovery from EAE (38). Here, we demonstrate that unlike in mice, PDPN + T cells induced under classic Th17-polarizing conditions express transcription factors associated with Th17 cells but do not produce IL-17.…”

“…In a transgenic mouse model of forced PDPN expression, cells isolated from the CNS possessed a higher percentage of IL-10 + CD4 + T cells than wild-type mice (38). Recent work also suggests that IL-10 expression is a response to CLEC-2/PDPN interaction; increases in IL-10 production from unstimulated naive CD4 + T cells were observed after cells were cultured with soluble CLEC-2 for 6 days (57).…”

Podoplanin promotes malignancy through a diversity of strategies

“…dendritic cells, a subset of macrophages, and effector T cells during acute inflammation [1][2][3] . In fact, the only function assigned to PDPN in normal adult tissues is related to lymphoid organs and the immune response [3][4][5] .…”

“…In fact, the only function assigned to PDPN in normal adult tissues is related to lymphoid organs and the immune response [3][4][5] . PDPN null mice die immediately after birth due to respiratory problems.…”