title: CD47 fusion protein targets CD172a+ cells in Crohn's disease and dampens the production of IL-1β and TNF.
abstract: In mice, the transfer of CD172a(+) (SIRP-α) dendritic cells (DCs) elicits T cell-driven colitis, whereas treatment with CD47-Fc protein, a CD172a-binding agent, confers protection. The aim of this study was to elucidate the nature and functional properties of human CD172a(+) DCs in chronic intestinal inflammation. Here, we show that CD172a(+)CD11c(+) cells accumulate in the mesenteric lymph nodes (mLNs) and inflamed intestinal mucosa in patients with Crohn's disease (CD). These cells are distinct from resident DCs and may coexpress markers typically associated with monocyte-derived inflammatory DCs such as CD14 and/or DC-SIGN, E-Cadherin, and/or CX3CR1. Spontaneous IL-1β and TNF production by HLA-DR(+) cells in CD tissues is restricted to those expressing CD172a. An avidity-improved CD47 fusion protein (CD47-Var1) suppresses the release of a wide array of inflammatory cytokines by CD172a(+) cells, which may include HLA-DR(-)CD172a(+) neutrophils, in inflamed colonic explant cultures and impairs the ability of HLA-DR(+)CD172a(+) cells to activate memory Th17 but not Th1 responses in mLNs. In conclusion, targeting CD172a(+) cells may represent novel therapeutic perspectives for patients with CD.
authors.affiliation: Immunoregulation Laboratory, The Research Center of the Centre Hospitalier de L'Université de Montréal (CRCHUM), Montreal, Canada.
authors.forename: Nobuyasu
authors.initials: N
authors.lastname: Baba
authors.forename: Vu Quang
authors.initials: VQ
authors.lastname: Van
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakahara
authors.forename: Manuel
authors.initials: M
authors.lastname: Rubio
authors.forename: Geneviève
authors.initials: G
authors.lastname: Fortin
authors.forename: Benoît
authors.initials: B
authors.lastname: Panzini
authors.forename: Geneviève
authors.initials: G
authors.lastname: Soucy
authors.forename: Ramses
authors.initials: R
authors.lastname: Wassef
authors.forename: Carole
authors.initials: C
authors.lastname: Richard
authors.forename: Raja
authors.initials: R
authors.lastname: Tamaz
authors.forename: Raymond
authors.initials: R
authors.lastname: Lahaie
authors.forename: Edmond-Jean
authors.initials: EJ
authors.lastname: Bernard
authors.forename: Yves
authors.initials: Y
authors.lastname: Caussignac
authors.forename: Raymond
authors.initials: R
authors.lastname: Leduc
authors.forename: Rasmy
authors.initials: R
authors.lastname: Lougnarath
authors.forename: Carole
authors.initials: C
authors.lastname: Bergeron
authors.forename: Marc-André
authors.initials: MA
authors.lastname: Racicot
authors.forename: Fanny
authors.initials: F
authors.lastname: Bergeron
authors.forename: Marie-Andrée
authors.initials: MA
authors.lastname: Panzini
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.forename: Denis
authors.initials: D
authors.lastname: Franchimont
authors.forename: Knut
authors.initials: K
authors.lastname: Schäkel
authors.forename: Gisbert
authors.initials: G
authors.lastname: Weckbecker
authors.forename: Frank
authors.initials: F
authors.lastname: Kolbinger
authors.forename: Christoph
authors.initials: C
authors.lastname: Heusser
authors.forename: Thomas
authors.initials: T
authors.lastname: Huber
authors.forename: Karl
authors.initials: K
authors.lastname: Welzenbach
authors.forename: Marika
authors.initials: M
authors.lastname: Sarfati
mesh_terms: D000943:Antigens, Differentiation / Q000378:metabolism*; D051928:CD47 Antigen / Q000378:metabolism*; D000073883:CX3C Chemokine Receptor 1; D015820:Cadherins / Q000378:metabolism; D003424:Crohn Disease / Q000276:immunology*; D003713:Dendritic Cells / Q000378:metabolism; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D051928:CD47 Antigen; C497894:CD47 protein, human; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D015820:Cadherins; D006684:HLA-DR Antigens; D053583:Interleukin-1beta; D019707:Receptors, Chemokine; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C501920:SIRPA protein, human; D014409:Tumor Necrosis Factor-alpha