title: Receptor activating NF-κB ligand (RANKL) is a constitutive intracellular protein in resting human basophils and is strongly induced on their surface by interleukin 3.
abstract: Receptor activating NF-κB ligand (RANKL) is a member of the TNF superfamily that plays a pivotal role in bone homeostasis as being the major osteoclastogenesis factor. RANKL also has pleiotropic effects in the immune system in which it is expressed by activated T and B cells and some innate lymphoid cells. RANKL-RANK interactions mediate lymph node organogenesis and immunoregulatory functions in autoimmune disease and carcinogenesis as well as cross talk between the immune system and bone. In this study, we show that basophils were the strongest RANKL mRNA-expressing cells amongst major leukocyte subsets in human blood. RANKL was preformed as an intracellular protein in resting basophils and was rapidly and strongly expressed on their surface upon stimulation with IL-3, but not other stimuli. This expression was stable for at least 6 days. Activated basophils could also release soluble RANKL in small quantities upon interaction with DCs or monocytes. In the blood, basophils were the sole cells to express membrane RANKL in response to IL-3. This study indicates that basophils should be considered as new players in the pleiotropic and complex RANKL-RANK interaction system and suggests a role for RANKL in the interaction between basophils and immune cells in inflammatory allergic tissues and secondary lymphoid organs.
authors.affiliation: CHU Nantes, Center for Immunomonitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, Nantes F-44000, France; Université de Nantes, Faculté de Médecine, Nantes F-44000, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Poli
authors.affiliation: CHU Nantes, Center for Immunomonitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, Nantes F-44000, France; Université de Nantes, Faculté de Médecine, Nantes F-44000, France; INSERM Center of Research in Transplantation and Immunology, UMR1064, Nantes F-44000, France; CHU Nantes, ITUN, Nantes F-44000, France.
authors.forename: Jérôme C
authors.initials: JC
authors.lastname: Martin
authors.affiliation: CHU Nantes, Center for Immunomonitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, Nantes F-44000, France; Université de Nantes, Faculté de Médecine, Nantes F-44000, France; INSERM Center of Research in Transplantation and Immunology, UMR1064, Nantes F-44000, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Braudeau
authors.affiliation: Université de Nantes, Faculté de Médecine, Nantes F-44000, France; INSERM Center of Research in Transplantation and Immunology, UMR1064, Nantes F-44000, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Bériou
authors.affiliation: CHU Nantes, Center for Immunomonitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, Nantes F-44000, France; Université de Nantes, Faculté de Médecine, Nantes F-44000, France; INSERM Center of Research in Transplantation and Immunology, UMR1064, Nantes F-44000, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Hémont
authors.affiliation: INSERM, Physiopathologie de la résorption osseuse et thérapie des tumeurs osseuses primitives, UMR957, Nantes F-44000, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Charrier
authors.affiliation: Université de Nantes, Faculté de Médecine, Nantes F-44000, France; CHU Nantes, ITUN, Nantes F-44000, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Guérin
authors.affiliation: Université de Nantes, Faculté de Médecine, Nantes F-44000, France; INSERM Center of Research in Transplantation and Immunology, UMR1064, Nantes F-44000, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Heslan
authors.affiliation: CHU Nantes, Center for Immunomonitoring Nantes Atlantic (CIMNA), Laboratoire d'Immunologie, Nantes F-44000, France; Université de Nantes, Faculté de Médecine, Nantes F-44000, France; INSERM Center of Research in Transplantation and Immunology, UMR1064, Nantes F-44000, France; CHU Nantes, ITUN, Nantes F-44000, France. Electronic address: Regis.josien@univ-nantes.fr.
authors.forename: Régis
authors.initials: R
authors.lastname: Josien
mesh_terms: D001491:Basophils / Q000276:immunology*; D001862:Bone Resorption / Q000276:immunology*; D002450:Cell Communication; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D007377:Interleukin-3 / Q000276:immunology; D042541:Intracellular Space / Q000378:metabolism*; D010010:Osteoclasts / Q000502:physiology*; D021381:Protein Transport / Q000276:immunology; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007377:Interleukin-3; D053245:RANK Ligand
keywords: Basophils; Interleukin-3; TNFSF11