An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD

Brynjólfsson, Siggeir F.; Magnusson, Maria K.; Kong, Philip; Jensen, Teis; Kuijper, Joseph L.; Håkansson, Katarina; Read, Christine B.; Stennicke, Vibeke W.; Sjövall, Henrik; Wick, Mary Jo

doi:10.1097/mib.0000000000000822

Cited by 21 publications

(29 citation statements)

References 29 publications

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“…TREM-1 activation leads to the secretion of pro-inflammatory cytokines and chemokines such as TNF, IL-6, IL-1β, IL-8 and CCL2, and synergizes with TLR activation (251)(252)(253)(254). Our group and another showed that intestinal mature Mfs expressed less TREM-1 than immature Mfs and blood monocytes (253,255), which has been corroborated by a recent study using scRNA-Seq (228) (Figure 6). The decrease of TREM-1 expression during Mf maturation seems to be due to the intestinal anti-inflammatory microenvironment, as monocytes cultured in the presence of IL-10 and TGF-β have reduced TREM-1 expression (253).…”

Section: Function Of Intestinal Mucosa Macrophagessupporting

confidence: 85%

“…As described above, TREM-1 is an inflammationamplifying receptor expressed on myeloid cells; it is involved in immune responses triggered by bacteria (249,250), yet its role in IBD is poorly understood. Our group showed that an anti-TREM-1 antagonist antibody dampened secretion of several proinflammatory cytokines and chemokines by LP cells from highly inflamed intestinal mucosa of IBD patients (255), supporting a potential role of TREM-1 in perpetuating intestinal inflammation in IBD patients.…”

Section: Function Of Intestinal Mucosa Macrophagesmentioning

confidence: 55%

“…Additional mechanisms that amply inflammation may also contribute to IBD pathogenesis. For example, the frequency and the number of TREM-1 + Mfs, which are mainly immature Mfs, are increased in IBD patients, especially in active lesion areas (254,255). As described above, TREM-1 is an inflammationamplifying receptor expressed on myeloid cells; it is involved in immune responses triggered by bacteria (249,250), yet its role in IBD is poorly understood.…”

Section: Function Of Intestinal Mucosa Macrophagesmentioning

confidence: 99%

“…Indeed, it has been shown that TREM-1 plays a role in initial signaling toward an inflammatory state of newly recruited monocytes in a mouse model of small intestine inflammation (351), and inhibition of TREM-1/CLEC5A pathways reduced intestinal inflammation during colitis (254,352). In humans, TREM-1 + Mfs are increased in IBD patients and its engagement enhanced pro-inflammatory cytokine secretion while a TREM-1 antagonist dampened it (254,255). Finally, Verstockt et al have shown that low TREM-1 expression in both whole blood and intestinal mucosa can predict anti-TNF therapy responders (353,354).…”

Section: Monocytes and Macrophagesmentioning

confidence: 99%

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Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Caër

Wick

2020

Front. Immunol.

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Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a complex immune-mediated disease of the gastrointestinal tract that increases morbidity and negatively influences the quality of life. Intestinal mononuclear phagocytes (MNPs) have a crucial role in maintaining epithelial barrier integrity while controlling pathogen invasion by activating an appropriate immune response. However, in genetically predisposed individuals, uncontrolled immune activation to intestinal flora is thought to underlie the chronic mucosal inflammation that can ultimately result in IBD. Thus, MNPs are involved in fine-tuning mucosal immune system responsiveness and have a critical role in maintaining homeostasis or, potentially, the emergence of IBD. MNPs include monocytes, macrophages and dendritic cells, which are functionally diverse but highly complementary. Despite their crucial role in maintaining intestinal homeostasis, specific functions of human MNP subsets are poorly understood, especially during diseases such as IBD. Here we review the current understanding of MNP ontogeny, as well as the recently identified human intestinal MNP subsets, and discuss their role in health and IBD.

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Section: Function Of Intestinal Mucosa Macrophagessupporting

confidence: 85%

Section: Function Of Intestinal Mucosa Macrophagesmentioning

confidence: 55%

Section: Function Of Intestinal Mucosa Macrophagesmentioning

confidence: 99%

Section: Monocytes and Macrophagesmentioning

confidence: 99%

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Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Caër

Wick

2020

Front. Immunol.

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“…Peptidoglycan recognition protein -1 (PGRP-1) only or linked to its ligand -peptidoglycans (PG) 40 was found to induce TREM-1 signaling and the synergetic interaction with TLRs 41,42 [43][44][45] .…”

Section: Trem-1 Ligandsmentioning

confidence: 99%

TREM-1; is It a Pivotal Target for Cardiovascular Diseases?

Kouassi

Gunasekar

Agrawal

et al. 2018

Preprint

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Cardiovascular Diseases (CVDs) are still menacing and killing adults worldwide, notwithstanding the tremendous effort, to decrease their related mortality and morbidity. Lately, a growing body of evidences indicated that inflammation plays a pivotal role in the pathogenesis and complications of CVDs. A receptor of the immunoglobulin superfamily, triggering receptor expressed on myeloid cells -1 (TREM-1) was shown to induce and to amplify the inflammation in both acute and chronic diseases pathogenesis and progression and hence it is one of the important factors that complicates CVDs. Thus, studies endeavored to investigate the role played by TREM-1 in CVDs with respect to their etiologies, complications and possible therapeutics. We examined here, for the first time, the most relevant studies regarding TREM-1 involvement in CVDs. We summarized the finding after critically analyzing them and made some suggestions for furtherance of the investigations with the aim to utilize TREM-1 and its pathways for diagnostic, management and prognosis of CVDs. Overall, TREM-1 was found to be involved in the pathogenesis of acute and chronic cardiovascular conditions like Acute myocardial infraction (AMI) and atherosclerosis as well. Although most therapeutic approaches are yet to be elucidated, present research outcome displays a promising future to utilize TREM-1 pathway as potential target to understand and manage CVDs.

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MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn´s Disease Patients

et al. 2022

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Inflammasomes are intracellular protein complexes whose activation results in proinflammatory cytokines. Inflammasomes are implicated in Crohn´s disease (CD) pathogenesis, yet the contribution of inflammasomes in intestinal epithelial cells (IECs) versus lamina propria (LP) macrophages is poorly understood. Whether inflammasome expression in intestinal tissue reflects the serum inflammatory protein profile of patients is also not known. We aimed to determine the intestinal cell types where inflammasome expression is increased in CD and if they correlate with the serum protein profile. RT-PCR and NanoString nCounter technology were used to characterize inflammasome gene expression in CD patients and controls. The mucosa, LP and IEC cell fractions and FACS-sorted cells were analyzed. Proximity extension assay with a 92-protein panel was used to determine the serum inflammatory protein profile. Compositional analysis was used to correlate ileum inflammasome gene expression with intestinal mononuclear phagocyte populations. We show that NLRP3 and MEFV inflammasome sensors and downstream effector expression including IL-1β are increased in inflamed mucosa of IBD patients and correlate with disease activity. Inflammasome gene expression increased with the abundance of immature intestinal macrophages, and increased IL-1β released by CD LP cells correlated with immature macrophage frequency. Inflammasome gene expression was also increased in circulating monocytes, the precursors of immature intestinal macrophages. Finally, the serum inflammatory profile of CD patients correlates with ileal expression of genes related to NLRP3 and MEFV inflammasomes. Overall, we show that MEFV and NLRP3 inflammasome expression in CD intestine is attributed to the accumulation of immature macrophages and correlates with serum inflammatory proteins.

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An Antibody Against Triggering Receptor Expressed on Myeloid Cells 1 (TREM-1) Dampens Proinflammatory Cytokine Secretion by Lamina Propria Cells from Patients with IBD

Abstract: An anti-TREM-1 antibody can dampen secretion of proinflammatory cytokines in inflamed patients with elevated PGLYRP-1. Moreover, PGLYRP-1 + myeloperoxidase is a potential biomarker for predicting the effect of anti-TREM-1 therapy.

Cited by 21 publications

References 29 publications

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

Human Intestinal Mononuclear Phagocytes in Health and Inflammatory Bowel Disease

TREM-1; is It a Pivotal Target for Cardiovascular Diseases?

MEFV and NLRP3 Inflammasome Expression Is Attributed to Immature Macrophages and Correlates with Serum Inflammatory Proteins in Crohn´s Disease Patients

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