title: Interleukin 34: a new modulator of human and experimental inflammatory bowel disease.
abstract: IBD (inflammatory bowel disease), where CD (Crohn's disease) and UC (ulcerative colitis) represent the two main forms, are chronic inflammatory conditions of the intestine. Macrophages play a central role in IBD pathogenesis and are regulated by major differentiation factors such as CSF-1 (colony-stimulating factor 1) in homoeostasis and inflammation. IL (interleukin)-34 has recently been discovered as a second ligand for CSF-1R (CSF-1 receptor). However, expression and involvement of IL-34 in IBD remain unknown. In the present paper, we investigated the expression of IL34, CSF1 and their shared receptor CSF1R in normal human ileum and colon, in inflamed and non-inflamed tissues of CD and UC patients, and in a mouse model of experimental colitis. We found distinct expression patterns of IL34 and CSF1 in ileum and colon, with higher IL34 in ileum and, in contrast, higher CSF1 in colon. Furthermore, IL34 and CSF1 expression was increased with inflammation in IBD patients and in experimental colitis. In humans, infiltrating cells of the lamina propria and intestinal epithelial cells expressed IL-34, and TNF-α (tumour necrosis factor α) regulated IL-34 expression in intestinal epithelial cells through the NF-κB (nuclear factor κB) pathway. These data demonstrate the expression pattern of IL-34 in ileum and colon and suggest IL-34 as a new modulator of inflammation in IBD.
authors.affiliation: *Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Alfred Nobels Allé 8, SE-141 52, Huddinge, Sweden.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Zwicker
authors.affiliation: *Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Alfred Nobels Allé 8, SE-141 52, Huddinge, Sweden.
authors.forename: Gisele L
authors.initials: GL
authors.lastname: Martinez
authors.affiliation: †Department of Cell and Molecular Biology, Karolinska Institutet, P.O. Box 285, SE-171 77, Stockholm, Sweden.
authors.forename: Madeleen
authors.initials: M
authors.lastname: Bosma
authors.affiliation: ‡Department of Biosciences and Nutrition, Karolinska Institutet, Novum, SE-141 52, Huddinge, Sweden.
authors.forename: Marco
authors.initials: M
authors.lastname: Gerling
authors.affiliation: *Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Alfred Nobels Allé 8, SE-141 52, Huddinge, Sweden.
authors.forename: Reuben
authors.initials: R
authors.lastname: Clark
authors.affiliation: *Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Alfred Nobels Allé 8, SE-141 52, Huddinge, Sweden.
authors.forename: Mirjam
authors.initials: M
authors.lastname: Majster
authors.affiliation: §Division of Medical Diagnostics, Ryhov County Hospital, Building E3 Level 4, SE-551 85, Jönköping, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Söderman
authors.affiliation: ║Department of Medicine Solna, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
authors.forename: Sven
authors.initials: S
authors.lastname: Almer
authors.affiliation: *Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, Alfred Nobels Allé 8, SE-141 52, Huddinge, Sweden.
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Boström
mesh_terms: D000818:Animals; D003093:Colitis, Ulcerative / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C552364:interleukin-34, mouse