Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells

Fuertbauer, Elke; Zaujec, Jan; Uhrín, Pavel; Raab, Ingrid; Weber, Michele; Schachner, Helga; Bauer, Miroslav; Schütz, Gerhard J.; Binder, Bernd R.; Sixt, Michael; Kerjaschki, Dontscho; Stockinger, Hannes

doi:10.1016/j.imlet.2013.07.007

Cited by 21 publications

(29 citation statements)

References 43 publications

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“…In contrast, Ccr7 −/− mice do show alterations in the development and intrathymic positioning of nTreg cells , consistent with the idea that conventional αβ T cells and developing nTreg cells share a requirement for CCR7 to enter the medulla. This scenario is also consistent with the diminished number of Foxp3 + nTreg cells in mice lacking podoplanin, a molecule that controls the intrathymic localization of CCL21, a ligand for CCR7 that is involved in thymocyte entry to the medulla . Interestingly however, nTreg‐cell numbers are not decreased in Ccr7 −/− mice .…”

Section: Foxp3+ Natural Regulatory T Cellssupporting

confidence: 77%

Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: What we learn from intrathymic migration

2015

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The organization of the thymus into distinct cortical and medullary regions enables it to control the step-wise migration and development of immature T-cell precursors. Such a process provides access to specialized cortical and medullary thymic epithelial cells at defined stages of maturation, ensuring the generation of self-tolerant and MHC-restricted conventional CD4+ and CD8+ αβ T cells. The migratory cues and stromal cell requirements that regulate the development of conventional αβ T cells have been well studied. However, the thymus also fosters the generation of several immunoregulatory T-cell populations that form key components of both innate and adaptive immune responses. These include Foxp3+ natural regulatory T cells, invariant γδ T cells, and CD1d-restricted invariant natural killer T cells (iNKT cells). While less is known about the intrathymic requirements of these nonconventional T cells, recent studies have highlighted the importance of the thymus medulla in their development. Here, we review recent findings on the mechanisms controlling the intrathymic migration of distinct T-cell subsets, and relate this to knowledge of the microenvironmental requirements of these cells.

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Section: Foxp3+ Natural Regulatory T Cellssupporting

confidence: 77%

Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: What we learn from intrathymic migration

2015

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“…Podoplanin, a mucin-type membrane glycoprotein rich in O-glycoside chains, 17 is mainly expressed on the lymphatic endothelium, 18 pneumocytes, 19 and glomerular podocytes 20 and plays essential roles in the development of lymphatic vessels, 21,22 cerebrovascular system formation and maintenance of its integrity, 23 as well as in the promotion of natural regulatory T cells. 24 Besides normal tissues and cells, PDPN is also found in human inflammatory diseases [25][26][27] and various cancer tissues 28 indicted by D2-40 staining technique or flow cytometry analysis. Previous studies have suggested that PDPN is not only expressed in cancer cells, 8 but also in cancer stroma, 9 especially in fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

The Detection of Plasma Soluble Podoplanin of Patients with Breast Cancer and Its Clinical Signification

Zhu

Zhao

et al. 2020

CMAR

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Background Podoplanin (PDPN) is a type-1 membrane sialoglycoprotein that is expressed in many cancer tumors including breast cancer; nonetheless, its roles in tumor occurrence, development, and metastasis are unclear. In this study, we aimed to investigate the clinical significance of plasma soluble PDPN (sPDPN) levels in patients with breast cancer and its significance in the diagnosis and metastasis. Materials and Methods Blood samples from healthy controls (CTL), patients with fibroadenomas of breast (FOB), and breast cancer (pathological type: invasive ductal carcinoma, IDC) were collected. sPDPN levels in the plasma of CTL and patients with FOB and IDC were measured by the ELISA. Results The plasma sPDPN levels in IDC patients (159 cases, 22.59±3.70 ng/mL) were higher than those in FOB patients (50 cases, 8.29±1.09 ng/mL; P <0.05) and CTL (100 cases, 1.21±0.12 ng/mL; P <0.0001). The sPDPN levels in patients at stage III and stage IV (30.08±4.66 ng/mL) were higher than in patients at stage I and stage II (11.84±1.12 ng/mL; P =0.005). The sPDPN levels in patients with high-moderate and moderate differentiation (17.50±3.02 ng/mL) were lower than those in patients with moderately low and low differentiation (35.73±4.26 ng/mL; P =0.026). The sPDPN levels in patients with metastasis (30.60±4.27 ng/mL) were much higher than those in patients without metastasis (13.02±1.30 ng/mL; P =0.017). Conclusion Plasma sPDPN may be used as a new marker for the determination of the clinical stage, differentiation degree, and metastasis status of breast cancer.

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“…The extracellular domain of podoplanin is shed from lymphatic endothelial cells into the perivascular stroma, forming a complex with the lymphatic-specific chemokine CCL21, which presumably attracts CCR7-positive immune cells toward the lymphatic vessels [25]. In addition, the podoplanin–CCL21 interaction in fibroblast-like reticular cells (FRCs) present in thymic conduits is associated with the development of specialized T cells [26]. CCL21 is also a potent chemoattractant in the tumor microenvironment, and its binding to podoplanin-expressing cancer-associated fibroblasts (CAFs) is involved in tumor immune escape [27].…”

Section: Podoplanin Structure and Protein Partnersmentioning

confidence: 99%

“…A second subset of CD4 + T cells, called adaptive Treg cells, develop as a consequence of activation of mature T cells during the adaptive immune response. The phenotype observed in Pdpn -deficient mice is apparently due to mislocalizacion of the chemokine CCL21 from the medulla to cortical areas of the thymus [26]. A population of thymic FRCs that form a conduit-like system in the medulla co-express podoplanin and CCL21, and the podoplanin–CCL21 interaction in these cells appears to be critical for the development of natural Treg cells along the cortical–medulla axis during early development and youth of wild-type mice [26].…”

Section: Podoplanin In Embryonic Development and Differentiationmentioning

confidence: 99%

Podoplanin in Inflammation and Cancer

Quintanilla

Montero-Montero

Renart

et al. 2019

IJMS

158

182

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Podoplanin is a small cell-surface mucin-like glycoprotein that plays a crucial role in the development of the alveoli, heart, and lymphatic vascular system. Emerging evidence indicates that it is also involved in the control of mammary stem-cell activity and biogenesis of platelets in the bone marrow, and exerts an important function in the immune response. Podoplanin expression is upregulated in different cell types, including fibroblasts, macrophages, T helper cells, and epithelial cells, during inflammation and cancer, where it plays important roles. Podoplanin is implicated in chronic inflammatory diseases, such as psoriasis, multiple sclerosis, and rheumatoid arthritis, promotes inflammation-driven and cancer-associated thrombosis, and stimulates cancer cell invasion and metastasis through a variety of strategies. To accomplish its biological functions, podoplanin must interact with other proteins located in the same cell or in neighbor cells. The binding of podoplanin to its ligands leads to modulation of signaling pathways that regulate proliferation, contractility, migration, epithelial–mesenchymal transition, and remodeling of the extracellular matrix. In this review, we describe the diverse roles of podoplanin in inflammation and cancer, depict the protein ligands of podoplanin identified so far, and discuss the mechanistic basis for the involvement of podoplanin in all these processes.

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Thymic medullar conduits-associated podoplanin promotes natural regulatory T cells

Cited by 21 publications

References 43 publications

Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: What we learn from intrathymic migration

Thymus medulla fosters generation of natural Treg cells, invariant γδ T cells, and invariant NKT cells: What we learn from intrathymic migration

The Detection of Plasma Soluble Podoplanin of Patients with Breast Cancer and Its Clinical Signification

Podoplanin in Inflammation and Cancer

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