title: CLEC-2 is required for development and maintenance of lymph nodes.
abstract: 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 Clec1b(fl/fl)PF4-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 Clec1b(fl/fl)PF4-Cre bone marrow, indicating that CLEC-2 expression in platelets was required for LN integrity. We demonstrated that LNs of Clec1b(fl/fl)PF4-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.
authors.affiliation: School of Immunity and Infection and.
authors.forename: Cécile
authors.initials: C
authors.lastname: Bénézech
authors.affiliation: School of Immunity and Infection and.
authors.forename: Saba
authors.initials: S
authors.lastname: Nayar
authors.affiliation: Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Brenda A
authors.initials: BA
authors.lastname: Finney
authors.affiliation: School of Immunity and Infection and.
authors.forename: David R
authors.initials: DR
authors.lastname: Withers
authors.affiliation: Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Lowe
authors.affiliation: School of Immunity and Infection and.
authors.forename: Guillaume E
authors.initials: GE
authors.lastname: Desanti
authors.affiliation: School of Immunity and Infection and.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Marriott
authors.affiliation: Centre for Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Steve P
authors.initials: SP
authors.lastname: Watson
authors.affiliation: School of Immunity and Infection and.
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Caamaño
authors.affiliation: School of Immunity and Infection and.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Buckley
authors.affiliation: School of Immunity and Infection and.
authors.forename: Francesca
authors.initials: F
authors.lastname: Barone
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004729:Endothelium, Lymphatic / Q000166:cytology / Q000378:metabolism; D017353:Gene Deletion; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D042583:Lymphangiogenesis; D008533:Megakaryocytes / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: C529518:CLEC-2 protein, mouse; D037181:Lectins, C-Type