title: Reprogramming of monocytes by GM-CSF contributes to regulatory immune functions during intestinal inflammation.
abstract: Human and murine studies showed that GM-CSF exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF-activated monocytes (GMaMs) in vivo. We used microarray technology and functional assays to characterize GMaMs in vitro and used a mouse model of colitis to study GMaM functions in vivo. GM-CSF activates monocytes to increase adherence, migration, chemotaxis, and oxidative burst in vitro, and primes monocyte response to secondary microbial stimuli. In addition, GMaMs accelerate epithelial healing in vitro. Most important, in a mouse model of experimental T cell-induced colitis, GMaMs show therapeutic activity and protect mice from colitis. This is accompanied by increased production of IL-4, IL-10, and IL-13, and decreased production of IFN-γ in lamina propria mononuclear cells in vivo. Confirming this finding, GMaMs attract T cells and shape their differentiation toward Th2 by upregulating IL-4, IL-10, and IL-13 in T cells in vitro. Beneficial effects of GM-CSF in Crohn's disease may possibly be mediated through reprogramming of monocytes to simultaneously improved bacterial clearance and induction of wound healing, as well as regulation of adaptive immunity to limit excessive inflammation.
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany; Interdisciplinary Center of Clinical Research, University Hospital Münster, Münster 48149, Germany; Gastrointestinal Research in Inflammation & Pathology, Murdoch Children's Research Institute, The Royal Children's Hospital Melbourne, Parkville 3052, Victoria, Australia; Department of Pediatrics, University of Melbourne, Melbourne Medical School, Parkville 3052, Victoria, Australia; Jan.Daebritz@uni-muenster.de.
authors: Jan
authors: J
authors: Däbritz
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany;
authors: Toni
authors: T
authors: Weinhage
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany;
authors: Georg
authors: G
authors: Varga
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany;
authors: Timo
authors: T
authors: Wirth
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany;
authors: Karoline
authors: K
authors: Walscheid
authors: Department of Dermatology, University Hospital Münster, Münster 48149, Germany; Institute of Immunology, University Hospital Münster, Münster 48149, Germany; and.
authors: Anne
authors: A
authors: Brockhausen
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany;
authors: David
authors: D
authors: Schwarzmaier
authors: Department of Medicine B, University Hospital Münster, Münster 48149, Germany.
authors: Markus
authors: M
authors: Brückner
authors: Department of Medicine B, University Hospital Münster, Münster 48149, Germany.
authors: Matthias
authors: M
authors: Ross
authors: Department of Medicine B, University Hospital Münster, Münster 48149, Germany.
authors: Dominik
authors: D
authors: Bettenworth
authors: Interdisciplinary Center of Clinical Research, University Hospital Münster, Münster 48149, Germany; Institute of Immunology, University Hospital Münster, Münster 48149, Germany; and.
authors: Johannes
authors: J
authors: Roth
authors: Interdisciplinary Center of Clinical Research, University Hospital Münster, Münster 48149, Germany; Department of Dermatology, University Hospital Münster, Münster 48149, Germany;
authors: Jan M
authors: JM
authors: Ehrchen
authors: Department of Pediatric Rheumatology and Immunology, University Children's Hospital Münster, Münster 48149, Germany; Interdisciplinary Center of Clinical Research, University Hospital Münster, Münster 48149, Germany;
authors: Dirk
authors: D
authors: Foell
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D019264:Adoptive Transfer; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003092:Colitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D007420:Intestine, Large / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D061251:Primary Cell Culture; D016897:Respiratory Burst / Q000187:drug effects; D055760:SOXF Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation
chemical_list: C556062:IL10 protein, mouse; C508598:IL4 protein, human; D018793:Interleukin-13; D055760:SOXF Transcription Factors; C490653:Sox18 protein, mouse; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor