dc.contributor |
Landspitali - The National University Hospital of Iceland |
dc.contributor.author |
Caër, Charles |
dc.contributor.author |
Gorreja, Frida |
dc.contributor.author |
Forsskåhl, Sophia K. |
dc.contributor.author |
Brynjólfsson, Siggeir Fannar |
dc.contributor.author |
Szeponik, Louis |
dc.contributor.author |
Magnusson, Maria K. |
dc.contributor.author |
Börjesson, Lars G. |
dc.contributor.author |
Block, Mattias |
dc.contributor.author |
Bexe-Lindskog, Elinor |
dc.contributor.author |
Wick, Mary Jo |
dc.date.accessioned |
2022-01-22T01:02:05Z |
dc.date.available |
2022-01-22T01:02:05Z |
dc.date.issued |
2021-02-04 |
dc.identifier.citation |
Caër , C , Gorreja , F , Forsskåhl , S K , Brynjólfsson , S F , Szeponik , L , Magnusson , M K , Börjesson , L G , Block , M , Bexe-Lindskog , E & Wick , M J 2021 , ' TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn's Disease Patients ' , Journal of Crohn's & colitis , vol. 15 , no. 8 , pp. 1346-1361 . https://doi.org/10.1093/ecco-jcc/jjab022 |
dc.identifier.issn |
1873-9946 |
dc.identifier.other |
38540788 |
dc.identifier.other |
63ad870e-e212-40f0-b403-b858d54be158 |
dc.identifier.other |
85113712440 |
dc.identifier.other |
33537747 |
dc.identifier.other |
unpaywall: 10.1093/ecco-jcc/jjab022 |
dc.identifier.uri |
https://hdl.handle.net/20.500.11815/2853 |
dc.description |
This work was funded by grants to M.J.W. from the Swedish Cancer Society [CAN2015/463 and CAN 2018/372] and to E.B.L. from the Swedish Government under the ALF agreement [ALFGBG-784211]. Publisher Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. |
dc.description.abstract |
BACKGROUND AND AIMS: Uncontrolled activation of intestinal mononuclear phagocytes [MNPs] drives chronic inflammation in inflammatory bowel disease [IBD]. Triggering receptor expressed on myeloid cells 1 [TREM-1] has been implicated in the pathogenesis of IBD. However, the role of TREM-1+ cell subsets in driving IBD pathology and the link with clinical parameters are not understood. We investigated TREM-1 expression in human intestinal MNP subsets and examined blocking TREM-1 as a potential IBD therapy. METHODS: TREM-1 gene expression was analysed in intestinal mucosa, enriched epithelial and lamina propria [LP] layers, and purified cells from controls and IBD patients. TREM-1 protein on immune cells was assessed by flow cytometry and immunofluorescence microscopy. Blood monocyte activation was examined by large-scale gene expression using a TREM-1 agonist or LP conditioned media [LP-CM] from patients in the presence or absence of TREM-1 and tumour necrosis factor [TNF] antagonist antibodies. RESULTS: TREM-1 gene expression increases in intestinal mucosa from IBD patients and correlates with disease score. TREM-1+ cells, which are mainly immature macrophages and CD11b+ granulocytes, increase among LP cells from Crohn's disease patients and their frequency correlates with inflammatory molecules in LP-CM. LP-CM from Crohn's disease patients induces an inflammatory transcriptome in blood monocytes, including increased IL-6 expression, which is reduced by simultaneous blocking of TREM-1 and TNF. CONCLUSIONS: High intestinal TREM-1 expression, reflecting a high frequency of TREM-1+ immature macrophages and TREM-1+CD11b+ granulocytes, is linked to the deleterious inflammatory microenvironment in IBD patients. Therefore, blocking the TREM-1 pathway, especially simultaneously with anti-TNF therapy, has potential as a new IBD therapy. |
dc.format.extent |
16 |
dc.format.extent |
753728 |
dc.format.extent |
1346-1361 |
dc.language.iso |
en |
dc.relation.ispartofseries |
Journal of Crohn's & colitis; 15(8) |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Bólgur |
dc.subject |
Crohns-sjúkdómur |
dc.subject |
Smáþarmar |
dc.subject |
Crohn’s disease |
dc.subject |
IL-6 |
dc.subject |
intestinal inflammation |
dc.subject |
macrophages |
dc.subject |
TNF |
dc.subject |
TREM-1 |
dc.subject |
Gene Expression |
dc.subject |
Humans |
dc.subject |
Macrophages/metabolism |
dc.subject |
Middle Aged |
dc.subject |
Crohn Disease/pathology |
dc.subject |
Granulocytes/metabolism |
dc.subject |
Male |
dc.subject |
CD11b Antigen/metabolism |
dc.subject |
Case-Control Studies |
dc.subject |
Young Adult |
dc.subject |
Triggering Receptor Expressed on Myeloid Cells-1/metabolism |
dc.subject |
Interleukin-6/metabolism |
dc.subject |
Intestinal Mucosa/metabolism |
dc.subject |
Aged, 80 and over |
dc.subject |
Adult |
dc.subject |
Female |
dc.subject |
Aged |
dc.subject |
Monocytes/metabolism |
dc.subject |
Gastroenterology |
dc.title |
TREM-1+ Macrophages Define a Pathogenic Cell Subset in the Intestine of Crohn's Disease Patients |
dc.type |
/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article |
dc.description.version |
Peer reviewed |
dc.identifier.doi |
10.1093/ecco-jcc/jjab022 |
dc.relation.url |
http://www.scopus.com/inward/record.url?scp=85113712440&partnerID=8YFLogxK |
dc.contributor.department |
Faculty of Medicine |
dc.contributor.department |
Clinical Laboratory Services, Diagnostics and Blood Bank |