CLEC-2 is required for development and maintenance of lymph nodes

The importance of CLEC-2, a natural ligand/receptor for Gp38/Podoplanin, in the formation of the lymphatic vasculature has recently been demonstrated. As the development and maintenance of lymph nodes (LNs) is dependent on the formation of the lymphatic vasculature and the differentiation of Gp38/Po...

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Published inBlood Vol. 123; no. 20; pp. 3200 - 3207
Main Authors Bénézech, Cécile, Nayar, Saba, Finney, Brenda A., Withers, David R., Lowe, Kate, Desanti, Guillaume E., Marriott, Clare L., Watson, Steve P., Caamaño, Jorge H., Buckley, Christopher D., Barone, Francesca
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 15.05.2014
American Society of Hematology
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Summary:The importance of CLEC-2, a natural ligand/receptor for Gp38/Podoplanin, in the formation of the lymphatic vasculature has recently been demonstrated. As the development and maintenance of lymph nodes (LNs) is dependent on the formation of the lymphatic vasculature and the differentiation of Gp38/Podoplanin+ stromal cells, we investigated the role of CLEC-2 in lymphoneogenesis and LN homeostasis. Using constitutive Clec1b−/− mice, we showed that while CLEC-2 was not necessary for initiation of the LN anlage, it was required at late stages of development. Constitutive deletion of CLEC-2 induced a profound defect in lymphatic endothelial cell proliferation, resulting in lack of LNs at birth. In contrast, conditional deletion of CLEC-2 in the megakaryocyte/platelet lineage in Clec1bfl/flPF4-Cre mice led to the development of blood-filled LNs and fibrosis, in absence of a proliferative defect of the lymphatic endothelial compartment. This phenotype was also observed in chimeric mice reconstituted with Clec1bfl/flPF4-Cre bone marrow, indicating that CLEC-2 expression in platelets was required for LN integrity. We demonstrated that LNs of Clec1bfl/flPF4-Cre mice are able to sustain primary immune responses but show a defect in immune cell recirculation after repeated immunizations, thus suggesting CLEC-2 as target in chronic immune response. •CLEC-2 is necessary for lymphatic cell proliferation and lymph node anlage persistence after birth.•Lack of CLEC-2 expression on megakaryocytes and platelets compromises lymph node integrity in adult life.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2013-03-489286