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CD14(hi) HLA-DRdim macrophages, with a resemblance to classical blood monocytes, dominate inflamed mucosa in Crohn's disease

Thiesen, Susanne LU ; Janciauskiene, Sabina; Uronen-Hansson, Heli LU ; Agace, William LU ; Hogerkorp, Carl-Magnus; Spee, Pieter; Hakansson, Katarina and Grip, Olof LU (2014) In Journal of Leukocyte Biology 95(3). p.531-541
Abstract
The increase of CD14(+) lamina propria macrophages in active Crohn's disease is due to a subset discriminated by HLA-DR, likely from CD16(-) blood monocytes. Intestinal M phi 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 phi, 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-DRdim cellular subset. This subset resembled the classical blood monocytes with low CD16, HLA-DR, and... (More)
The increase of CD14(+) lamina propria macrophages in active Crohn's disease is due to a subset discriminated by HLA-DR, likely from CD16(-) blood monocytes. Intestinal M phi 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 phi, 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-DRdim 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-DRdim subset. This enhances our understanding of CD pathology and may provide new options in treatment. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
myeloid cells, inflammation, cytokines, matrix metalloproteinases
in
Journal of Leukocyte Biology
volume
95
issue
3
pages
531 - 541
publisher
Society for Leukocyte Biology
external identifiers
  • wos:000335324400016
  • scopus:84899471444
ISSN
1938-3673
DOI
10.1189/jlb.0113021
language
English
LU publication?
yes
id
05ae9600-6711-4eb1-8303-ec9edd3a360f (old id 4559501)
date added to LUP
2014-08-01 07:44:25
date last changed
2017-11-19 03:14:03
@article{05ae9600-6711-4eb1-8303-ec9edd3a360f,
  abstract     = {The increase of CD14(+) lamina propria macrophages in active Crohn's disease is due to a subset discriminated by HLA-DR, likely from CD16(-) blood monocytes. Intestinal M phi 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 phi, 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-DRdim 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-DRdim subset. This enhances our understanding of CD pathology and may provide new options in treatment.},
  author       = {Thiesen, Susanne and Janciauskiene, Sabina and Uronen-Hansson, Heli and Agace, William and Hogerkorp, Carl-Magnus and Spee, Pieter and Hakansson, Katarina and Grip, Olof},
  issn         = {1938-3673},
  keyword      = {myeloid cells,inflammation,cytokines,matrix metalloproteinases},
  language     = {eng},
  number       = {3},
  pages        = {531--541},
  publisher    = {Society for Leukocyte Biology},
  series       = {Journal of Leukocyte Biology},
  title        = {CD14(hi) HLA-DRdim macrophages, with a resemblance to classical blood monocytes, dominate inflamed mucosa in Crohn's disease},
  url          = {http://dx.doi.org/10.1189/jlb.0113021},
  volume       = {95},
  year         = {2014},
}