ババ　ノブヤス   馬場　伸育    所属   川崎医科大学  医学部 基礎医学　免疫学    職種   講師
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	CD47 fusion protein targets CD172a+ cells in Crohn's disease and dampens the production of IL-1β and TNF.
掲載誌名	正式名：The Journal of experimental medicine 略　 称：J Exp Med ISSNコード：15409538/00221007
掲載区分	国外
巻・号・頁	210(6),pp.1251-63
著者・共著者	Nobuyasu Baba, Vu Quang Van, Keiko Wakahara, Manuel Rubio, Geneviève Fortin, Benoît Panzini, Geneviève Soucy, Ramses Wassef, Carole Richard, Raja Tamaz, Raymond Lahaie, Edmond-Jean Bernard, Yves Caussignac, Raymond Leduc, Rasmy Lougnarath, Carole Bergeron, Marc-André Racicot, Fanny Bergeron, Marie-Andrée Panzini, Pieter Demetter, Denis Franchimont, Knut Schäkel, Gisbert Weckbecker, Frank Kolbinger, Christoph Heusser, Thomas Huber, Karl Welzenbach, Marika Sarfati
発行年月	2013/06
概要	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.
DOI	10.1084/jem.20122037
PMID	23669395