Person:

Turley, Shannon J.

Podoplanin (PDPN) is a well-conserved, mucin-type transmembrane protein expressed in multiple tissues during ontogeny and in adult animals, including the brain, heart, kidney, lungs, osteoblasts, and lymphoid organs. Studies of PDPN-deficient mice have demonstrated that this molecule plays a critical role in development of the heart, lungs, and lymphatic system. PDPN is widely used as a marker for lymphatic endothelial cells and fibroblastic reticular cells of lymphoid organs and for lymphatics in the skin and tumor microenvironment. Much of the mechanistic insight into PDPN biology has been gleaned from studies of tumor cells; tumor cells often upregulate PDPN as they undergo epithelial-mesenchymal transition and this upregulation is correlated with increased motility and metastasis. The physiological role of PDPN that has been most studied is its ability to aggregate and activate CLEC-2-expressing platelets, as PDPN is the only known endogenous ligand for CLEC-2. However, more recent studies have revealed that PDPN also plays crucial roles in the biology of immune cells, including T cells and dendritic cells. This review will provide a comprehensive overview of the diverse roles of PDPN in development, immunology, and cancer.

Lymph node stromal cells (LNSCs) closely regulate immunity and self-tolerance, yet key aspects of their biology remain poorly illuminated. Comparative transcriptomic analyses of murine LNSC subsets revealed expression of important immune mediators, growth factors, and novel structural components. Pairwise analyses of ligands and cognate receptors across hematopoietic and stromal subsets suggested a complex web of cross-talk. Compared with skin and thymic fibroblasts, fibroblastic reticular cells (FRCs) were enriched in genes relevant to cytokine signaling. LNSCs from inflamed lymph nodes upregulated acute phase response genes, chemokines, and antigen presentation genes. Poorly studied podoplanin−CD31− LNSCs showed similarities to FRCs, but lacked IL-7 expression, and were identified as myofibroblastic integrin α7+ pericytes. Together these data comprehensively describe the transcriptional characteristics of LNSC subsets.