title: Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs.
abstract: Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell-cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c(+) DCs (Sirpa(Δ) (DC) ). Sirpa(Δ) (DC) mice manifested a marked reduction of CD4(+) CD8α(-) conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa(Δ) (DC) mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell-selective adhesion molecule (ESAM) or Epstein-Barr virus-induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM(+) or EBI2(+) cDCs were markedly reduced in the spleen of Sirpa(Δ) (DC) mice. Thus, our results suggest that SIRPα intrinsic to CD11c(+) DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.|Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Washio
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Takenori
authors.initials: T
authors.lastname: Kotani
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Datu
authors.initials: D
authors.lastname: Respatika
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Yoji
authors.initials: Y
authors.lastname: Murata
authors.affiliation: Department of Medicine and Clinical Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Okazawa
authors.affiliation: Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma, 371-8514, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukunaga
authors.affiliation: Division of Dermatology, Department of Internal Related, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nishigori
authors.affiliation: Division of Molecular and Cellular Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Kobe, 650-0017, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matozaki
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016827:CD8 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism*; D000078404:Epidermal Cells; D006706:Homeostasis; D008198:Lymph Nodes / Q000166:cytology; D008221:Lymphoid Tissue / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism*; D013154:Spleen / Q000166:cytology
chemical_list: D016827:CD8 Antigens; C409469:CD8 antigen, alpha chain; D015815:Cell Adhesion Molecules; C428190:Esam protein, mouse; C543809:Gpr183 protein, mouse; C501922:Sirpa protein, mouse; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic