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Blood, 15 March 2005, Vol. 105, No. 6, pp. 2245-2246. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Oldenborg, P.-A. Search for Related Content PubMed Articles by Oldenborg, P.-A. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Comment on Piccio et al, page 2421 CD47 and SIRPs: new openings Per-Arne Oldenborg UMEÅ UNIVERSITY In the present issue of Blood, Piccio and colleagues report that a member of the signal-regulatory protein (SIRP) family, SIRP2, is expressed by T cells, binds to CD47, and costimulates T-cell proliferation. Within the SIRP family of cell-surface glycoproteins, SIRP and SIRP1 have hitherto been identified and studied. SIRP is highly expressed by myeloid cells and neurons, but expression has also been found on endothelial cells and a subpopulation of B cells. In myeloid cells, SIRP has been reported to inhibit phagocytosis and cytokine production when ligated by its ubiquitously expressed cell-surface ligand CD47, a function mediated by the cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) of SIRP.1,2 The CD47-SIRP interaction can also support cell-cell adhesion and cell migration. SIRP1, on the other hand, does not have any intracellular signaling motifs of its own, but functions by signaling through recruitment of the adaptor protein DAP12, resulting in stimulation of myeloid cellular functions.3 In contrast to SIRP, SIRP1 does not seem to bind CD47.4 The present report on SIRP2 significantly extends the understanding of this family of receptors, showing that SIRP2, in contrast to SIRP and SIRP1, is not expressed by myeloid cells, but rather by T cells and activated natural killer (NK) cells. Similar to SIRP, SIRP2 binds CD47 on other cells, in this case antigen-presenting cells (APCs). However, the CD47 binding affinity is lower for SIRP2 than that for SIRP. The cytoplasmic domain of SIRP2 does not have ITIM motifs or the capacity to bind DAP12. Instead, the authors suggest that the SIRP2-CD47 interaction may function to strengthen the T-cell–APC binding, thereby supporting T-cell activation. These data are supported by a recent report, where the SIRP2 protein was referred to as SIRP, and shown to bind CD47.5 That study showed that, by binding to CD47, both SIRP2/SIRP and SIRP fusion proteins could induce CD47-dependent apoptosis in CD47-expressing cells.5 The present findings raise new, interesting questions about the ability of CD47 to regulate immune reactions by binding to SIRP and SIRP2. Although the APCs in the present study were B cells, which may not express SIRP, other important APCs such as dendritic cells and macrophages express this receptor. Bidirectional signaling following binding of CD47 on the T cell to SIRP on the APC was reported to inhibit both T-cell and APC activation.2 However, it has also been shown that this interaction might have the opposite effect, resulting in costimulation of T-cell activation.1,4 Since the CD47-SIRP interaction could theoretically operate in parallel with the SIRP2-CD47 interaction reported by Piccio et al (see figure), further investigations are needed to understand how these interactions can regulate T cells and APCs in various settings of immune activation. Possible effects of dual interactions between CD47-SIRP and CD47-SIRP2 upon contact between T cells and APCs.   References Brown EJ, Frazier WA. Integrin-associated protein (CD47) and its ligands. Trends Cell Biol. 2001;11: 130-135.[CrossRef][Medline] [Order article via Infotrieve] Latour S, Tanaka H, Demeure C, et al. Bidirectional negative regulation of human T and dendritic cells by CD47 and its cognate receptor signal-regulatory protein-alpha: down-regulation of IL-12 responsiveness and inhibition of dendritic cell activation. J Immunol. 2001;167: 2547-2554.[Abstract/Free Full Text] Hayashi A, Ohnishi H, Okazawa H, et al. Positive regulation of phagocytosis by SIRPbeta and its signaling mechanism in macrophages. J Biol Chem. 2004;279: 29450-29460.[Abstract/Free Full Text] Seiffert M, Brossart P, Cant C, et al. Signal-regulatory protein alpha (SIRPalpha) but not SIRPbeta is involved in T-cell activation, binds to CD47 with high affinity, and is expressed on immature CD34(+)CD38(-) hematopoietic cells. Blood. 2001;97: 2741-2749.[Abstract/Free Full Text] Brooke G, Holbrook JD, Brown MH, Barclay AN. Human lymphocytes interact directly with CD47 through a novel member of the signal regulatory protein (SIRP) family. J Immunol. 2004;173: 2562-2570.[Abstract/Free Full Text] CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Adhesion of human T cells to antigen-presenting cells through SIRP2-CD47 interaction costimulates T-cell proliferation Laura Piccio, William Vermi, Kent S. Boles, Anja Fuchs, Carey A. Strader, Fabio Facchetti, Marina Cella, and Marco Colonna Blood 2005 105: 2421-2427. [Abstract] [Full Text] [PDF] This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Oldenborg, P.-A. Search for Related Content PubMed Articles by Oldenborg, P.-A. 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