Elizabeth J. HainingKate L. LoweSurasak WichaiyoRaghu P. KataruZoltan NagyDean Pj KavanaghSian LaxYing DiBernhard NieswandtBenoît Ho-Tin-NoéBabak J. MehraraYotis A. SenisJulie RayesSteve P. WatsonRudolf Virchow CenterUniversité de StrasbourgUniversity of BirminghamMahidol UniversityMemorial Sloan-Kettering Cancer CenterInsermUniversities of Birmingham and Nottingham2020-03-262020-03-262020-01-01Platelets. (2020)13691635095371042-s2.0-85081231036https://repository.li.mahidol.ac.th/handle/123456789/53879© 2020, © 2020 Taylor & Francis Group, LLC. C-type lectin-like receptor 2 (CLEC-2) is considered as a potential drug target in settings of wound healing, inflammation, and infection. A potential barrier to this is evidence that CLEC-2 and its ligand podoplanin play a critical role in preventing lymphatic vessel blood filling in mice throughout life. In this study, this aspect of CLEC-2/podoplanin function is investigated in more detail using new and established mouse models of CLEC-2 and podoplanin deficiency, and models of acute and chronic vascular remodeling. We report that CLEC-2 expression on platelets is not required to maintain a barrier between the blood and lymphatic systems in unchallenged mice, post-development. However, under certain conditions of chronic vascular remodeling, such as during tumorigenesis, deficiency in CLEC-2 can lead to lymphatic vessel blood filling. These data provide a new understanding of the function of CLEC-2 in adult mice and confirm the essential nature of CLEC-2-driven platelet activation in vascular developmental programs. This work expands our understanding of how lymphatic blood filling is prevented by CLEC-2-dependent platelet function and provides a context for the development of safe targeting strategies for CLEC-2 and podoplanin.Mahidol UniversityMedicineArticleSCOPUS10.1080/09537104.2020.1734784