title: CD64 distinguishes macrophages from dendritic cells in the gut and reveals the Th1-inducing role of mesenteric lymph node macrophages during colitis.
abstract: Dendritic cells (DCs) and monocyte-derived macrophages (MΦs) are key components of intestinal immunity. However, the lack of surface markers differentiating MΦs from DCs has hampered understanding of their respective functions. Here, we demonstrate that, using CD64 expression, MΦs can be distinguished from DCs in the intestine of both mice and humans. On that basis, we revisit the phenotype of intestinal DCs in the absence of contaminating MΦs and we delineate a developmental pathway in the healthy intestine that leads from newly extravasated Ly-6C(hi)  monocytes to intestinal MΦs. We determine how inflammation impacts this pathway and show that T cell-mediated colitis is associated with massive recruitment of monocytes to the intestine and the mesenteric lymph node (MLN). There, these monocytes differentiate into inflammatory MΦs endowed with phagocytic activity and the ability to produce inducible nitric oxide synthase. In the MLNs, inflammatory MΦs are located in the T-cell zone and trigger the induction of proinflammatory T cells. Finally, T cell-mediated colitis develops irrespective of intestinal DC migration, an unexpected finding supporting an important role for MLN-resident inflammatory MΦs in the etiology of T cell-mediated colitis.
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, Marseille, France.
authors.forename: Samira
authors.initials: S
authors.lastname: Tamoutounour
authors.forename: Sandrine
authors.initials: S
authors.lastname: Henri
authors.forename: Hugues
authors.initials: H
authors.lastname: Lelouard
authors.forename: Béatrice
authors.initials: B
authors.lastname: de Bovis
authors.forename: Colin
authors.initials: C
authors.lastname: de Haar
authors.forename: C Janneke
authors.initials: CJ
authors.lastname: van der Woude
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Woltman
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Reyal
authors.forename: Dominique
authors.initials: D
authors.lastname: Bonnet
authors.forename: Dorine
authors.initials: D
authors.lastname: Sichien
authors.forename: Calum C
authors.initials: CC
authors.lastname: Bain
authors.forename: Allan McI
authors.initials: AM
authors.lastname: Mowat
authors.forename: Caetano
authors.initials: C
authors.lastname: Reis e Sousa
authors.forename: Lionel F
authors.initials: LF
authors.lastname: Poulin
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.forename: Martin
authors.initials: M
authors.lastname: Guilliams
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D006801:Humans; D018928:Immunity, Mucosal; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology* / Q000473:pathology; D008643:Mesentery / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D017452:Receptors, IgG / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D017452:Receptors, IgG