Mucosal IL-8 and TGF-β recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells

Smythies, Lesley E.; Maheshwari, Akhil; Clements, Ronald H.; Eckhoff, Devin E.; Novak, Lea; Vu, Huong; Mosteller-Barnum, L. Meg; Sellers, Marty T.; Smith, Phillip D.

doi:10.1189/jlb.1005566

Cited by 126 publications

(136 citation statements)

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“…In the inflamed intestinal lamina propria, the source of TNF-α and other proinflammatory cytokines has been localized to macrophages [34][35][36], which are derived from (and continually replenished by) circulating monocytes [37].…”

Section: What Is the Underlying Defect?mentioning

confidence: 99%

Crohn’s disease as an immunodeficiency

Hayee

Rahman

Sewell

et al. 2010

Expert Review of Clinical Immunology

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The pathogenesis of Crohn's disease (CD) has widely been regarded as the consequence of a dysregulated T-cell-mediated response to intestinal microbes, and the majority of the worldwide research effort has focused on characterizing and treating the chronic inflammatory phase of the disease. However, recent molecular biological and clinical investigations indicate that CD is actually a primary immunodeficiency. At first counter-intuitive, the apparent paradox of a pathogenic innate immune defect can be linked mechanistically to the granulomatous chronic inflammation characteristic of the disease. Genome-wide association studies have corroborated the involvement of innate immune dysfunction in the pathogenesis of CD, but less than 20% of the heritable risk is accounted for. By contrast, in vitro and in vivo stimulation of the immune system has highlighted novel areas of interest that may lead to the development of targeted therapeutic and diagnostic tools. Keywordsbacteria; Crohn's disease; immunodeficiency; innate immunity; macrophage; neutrophil Established intestinal lesions in Crohn's disease (CD) contain a massive, mixed inflammatory cell infiltrate associated with a complex storm of cytokines in a selfperpetuating, chronic inflammatory response [1][2][3]. Most research to date has focused on the the immunological characteristics of established lesions and drawn inferences about their initiation. The predominance of a classically Th1-associated cytokine profile in these lesions led to the assumption that T lymphocytes were central to the initial pathogenesis. More recently, the role of regulatory (Treg) FoxP3 + and IL-23-induced responsive Th17-type T lymphocytes has gained popularity [2,4,5]. Treg cell populations are diminished in patients with CD [6] and, although the hypothesis of CD as an immunodeficiency does not necessarily exclude defects in T-cell function, to date, no convincing intrinsic (primary) defect has been identified to implicate these cells in the pathogenesis of human CD.The hypothesis that immunodeficiency underpins the development of CD seems, at first, to be in direct contrast with histological observations of established intestinal lesions and the † Author for correspondence: Tel.: +44 207 679 6170 Fax: +44 207 679 0967 b.hayee@nhs.net. Financial & competing interests disclosure The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Europe PMC Funders Group Association between immunodeficiency diseases & CDThere is a well-known and strong association between primary immunodeficiency disorders and non-infectious granulomatous intestinal inflammation. Chronic granulomatous disease (CGD), glycogen storage disease type 1b, leukocyte adhesion deficiency, Chediak-Higashi and Hermansky-Pudlak syndromes are all strongly associated with intestinal inflammation that is indistinguishable from CD [...

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Section: What Is the Underlying Defect?mentioning

confidence: 99%

Crohn’s disease as an immunodeficiency

Hayee

Rahman

Sewell

et al. 2010

Expert Review of Clinical Immunology

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“…These chemokines are further subclassified on the basis of the presence or absence of an additional glutamate-leucine-arginine (ELR) motif into ELR ϩ CXC and the ELR Ϫ CXC groups (1). The vascular endothelium is an important source of ELR ϩ CXC chemokines, where these chemokines serve as important chemoattractants for neutrophils and monocytes and also play an important role in angiogenesis (3)(4)(5)(6). There are seven known ELR ϩ CXC chemokines in humans, including interleukin-8 (IL-8)/CXC ligand 8 (CXCL8), 2 growth-related oncoprotein (GRO)-␣/CXCL1, GRO-␤/CXCL2, GRO-␥/CXCL3, epithelialderived neutrophil attractant (ENA)-78/CXCL5, granulocyte chemotactic peptide (GCP)-2/CXCL6, and the neutrophil-activating peptide (NAP)-2/CXCL7 (2).…”

mentioning

confidence: 99%

“…There are seven known ELR ϩ CXC chemokines in humans, including interleukin-8 (IL-8)/CXC ligand 8 (CXCL8), 2 growth-related oncoprotein (GRO)-␣/CXCL1, GRO-␤/CXCL2, GRO-␥/CXCL3, epithelialderived neutrophil attractant (ENA)-78/CXCL5, granulocyte chemotactic peptide (GCP)-2/CXCL6, and the neutrophil-activating peptide (NAP)-2/CXCL7 (2). ELR ϩ CXC chemokines are critical regulators of leukocyte trafficking into inflamed tissues (4,5,7,10,11). For reasons that are not well elucidated, endothelial-leukocyte interaction and leukocyte emigration into the tissues is primarily concentrated in small vessels such as capillaries and post-capillary venules (8,9).…”

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confidence: 99%

Low Intensity Shear Stress Increases Endothelial ELR+ CXC Chemokine Production via a Focal Adhesion Kinase-p38β MAPK-NF-κB Pathway

Shaik

Soltau

Chaturvedi

et al. 2009

Journal of Biological Chemistry

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CXC chemokines with a glutamate-leucine-arginine (ELR) tripeptide motif (ELR؉ CXC chemokines) play an important role in leukocyte trafficking into the tissues. For reasons that are not well elucidated, circulating leukocytes are recruited into the tissues mainly in small vessels such as capillaries and venules. Because ELR ؉ CXC chemokines are important mediators of endothelial-leukocyte interaction, we compared chemokine expression by microvascular and aortic endothelium to investigate whether differences in chemokine expression by various endothelial types could, at least partially, explain the microvascular localization of endothelial-leukocyte interaction. Both in vitro and in vivo models indicate that ELR ؉ CXC chemokine expression is higher in microvascular endothelium than in aortic endothelial cells. These differences can be explained on the basis of the preferential activation of endothelial chemokine production by low intensity shear stress. Low shear activated endothelial ELR ؉ CXC chemokine production via cell surface heparan sulfates, ␤ 3 -integrins, focal adhesion kinase, the mitogen-activated protein kinase p38␤, mitogen-and stress-associated protein kinase-1, and the transcription factor.

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“…28 Thus, analyzing a model of MNCs stimulated with LPS is a logical focus for speculating the possible response of these cells to bacterial stimuli and their comparison between IBS patients and controls. Likewise, it is important to point out that in the 2 studies using a murine model, Bain et al 29 and Tamoutounour et al 16 proposed that the conditions of the intestine lead to the development of the macrophage in a cascade-like fashion.…”

Section: Discussionmentioning

confidence: 99%

Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome

Rodríguez-Fandiño

Hernández-Ruiz

López-Vidal

et al. 2017

J Neurogastroenterol Motil

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Background/AimsAbnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). The aim was to compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of Escherichia coli lipopolysaccharides (LPS), in vitro. MethodsMononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours. The maturation phenotype was examined by flow cytometry as follows: M1-Early (CD11c + CD206 -), M2-Advanced (CD11c -CD206 + CX3CR1 + ); expression of membrane markers was reported as mean fluorescence intensity (MFI). The Mann-Whitney test was used and significance was set at P < 0.05. ResultsIn CD14+ cells, CD11c expression decreased with vs without LPS both in IBS (MFI: 8766.0 ± 730.2 vs 12 920.0 ± 949.2, P < 0.001) and controls (8233.0 ± 613.9 vs 13 750.0 ± 743.3, P < 0.001). M1-Early cells without LPS, showed lower CD11c expression in IBS than controls (MFI: 11 540.0 ± 537.5 vs 13 860.0 ± 893.7, P = 0.040), while both groups showed less CD11c in response to LPS (P < 0.01). Furthermore, the percentage of "Intermediate" (CD11c + CD206 + CX3CR1 + ) cells without LPS, was higher in IBS than controls (IBS = 9.5 ± 1.5% vs C = 4.9 ± 1.4%, P < 0.001). Finally, fractalkine receptor (CX3CR1) expression on M2-Advanced cells was increased when treated with LPS in controls but not in IBS (P < 0.001). ConclusionsThe initial phase of monocyte/macrophage maturation appears to be more advanced in IBS compared to controls. However, the decreased CX3CR1 in patients with IBS, compared to controls, when stimulated with LPS suggests a state of immune activation in IBS.

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Mucosal IL-8 and TGF-β recruit blood monocytes: evidence for cross-talk between the lamina propria stroma and myeloid cells

Cited by 126 publications

References 40 publications

Crohn’s disease as an immunodeficiency

Crohn’s disease as an immunodeficiency

Low Intensity Shear Stress Increases Endothelial ELR+ CXC Chemokine Production via a Focal Adhesion Kinase-p38β MAPK-NF-κB Pathway

Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome

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