title: CD14(hi)HLA-DR(dim) macrophages, with a resemblance to classical blood monocytes, dominate inflamed mucosa in Crohn's disease.
abstract: Intestinal M play an important role in maintaining gut homeostasis. However, little is known about these cells, their precursors, and their role in intestinal inflammation. Here, we characterize the CD14(+) mononuclear cell populations in intestinal mucosa and blood in patients with CD. Among the LP CD14(+) M, we identified three distinct HLA-DR(+)-expressing subsets. Compared with uninflamed, inflamed mucosa contained a marked increase in the proportion of the CD14(hi)HLA-DR(dim) cellular subset. This subset resembled the classical blood monocytes with low CD16, HLA-DR, and CX3CR1 expression. Classical monocytes migrated efficiently toward CCL2 and released the highest levels of MMP-1 and proinflammatory cytokines when stimulated with immune complexes or LPS. Our findings strongly suggest that it is the classical and not the intermediate or nonclassical monocytes that are the precursors to the dominating intestinal CD14(hi)HLA-DR(dim) subset. This enhances our understanding of CD pathology and may provide new options in treatment.
authors.affiliation: 2.Lund University, Malmö, Sweden. olof.grip@med.lu.se.
authors.forename: Susanne
authors.initials: S
authors.lastname: Thiesen
authors.forename: Sabina
authors.initials: S
authors.lastname: Janciauskiene
authors.forename: Heli
authors.initials: H
authors.lastname: Uronen-Hansson
authors.forename: William
authors.initials: W
authors.lastname: Agace
authors.forename: Carl-Magnus
authors.initials: CM
authors.lastname: Högerkorp
authors.forename: Pieter
authors.initials: P
authors.lastname: Spee
authors.forename: Katarina
authors.initials: K
authors.lastname: Håkansson
authors.forename: Olof
authors.initials: O
authors.lastname: Grip
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D003424:Crohn Disease / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D018950:Lipopolysaccharide Receptors
keywords: cytokines; inflammation; matrix metalloproteinases; myeloid cells