title: Absence of CD47 in vivo influences thymic dendritic cell subset proportions but not negative selection of thymocytes.
abstract: CD47 is a ubiquitously expressed molecule which has been attributed a role in many cellular processes. Its role in preventing cellular phagocytosis has defined CD47 as an obligatory self-molecule providing a 'don't-eat-me-signal'. Additionally, CD47-CD172a interactions are important for cellular trafficking. Yet, the contribution of CD47 to T cell stimulation remains controversial, acting sometimes as a co-stimulator and sometimes as an inhibitor of TCR signalling or peripheral T cell responses. Most of the experiments leading to this controversy have been carried in in vitro systems. Moreover, the role of CD47 on thymocyte differentiation, which precisely relies on TCR signal strength, has not been evaluated. Here, we examine the in vivo role of CD47 in T cell differentiation using CD47-deficient mice. We find that, in the absence of CD47, thymocyte positive and negative selection processes are not altered. Indeed, our data demonstrate that the absence of CD47 does not influence the strength of TCR signalling in thymocytes. Furthermore, in agreement with a role for CD47-CD172a interactions in CD172a(+) dendritic cell migration, we report a reduced proportion of thymic dendritic cells expressing CD172a in CD47-deficient mice. As the total proportion of dendritic cells is maintained, this creates an imbalance in the proportion of CD172a(+) and CD172a(low) dendritic cells in the thymus. Together, these data indicate that the altered proportion of thymic dendritic cell subsets does not have a primordial influence on thymic selection processes.
authors.affiliation: Research Centre, Maisonneuve-Rosemont Hospital, Department of Microbiology and Immunology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Fanny
authors.initials: F
authors.lastname: Guimont-Desrochers
authors.forename: Claudine
authors.initials: C
authors.lastname: Beauchamp
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chabot-Roy
authors.forename: Véronique
authors.initials: V
authors.lastname: Dugas
authors.forename: Erin E
authors.initials: EE
authors.lastname: Hillhouse
authors.forename: Julie
authors.initials: J
authors.lastname: Dusseault
authors.forename: Geneviève
authors.initials: G
authors.lastname: Langlois
authors.forename: Patrick
authors.initials: P
authors.lastname: Gautier-Ethier
authors.forename: Jinane
authors.initials: J
authors.lastname: Darwiche
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lesage
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D017634:Self Tolerance; D015398:Signal Transduction / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000276:immunology*
chemical_list: D051928:CD47 Antigen; C501922:Sirpa protein, mouse; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic