CD163 and Inflammation: Biological, Diagnostic, and Therapeutic Aspects

Etzerodt, Anders; Moestrup, Søren K.

doi:10.1089/ars.2012.4834

Cited by 436 publications

(393 citation statements)

References 123 publications

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“…This analysis suggests that Treg cells may use two major sets of genes to modulate Teff gene responses in vitro: one counteracting Teff cell activation (zone A and D) and the other inducing an autoinhibitory mechanism (zone C). The five genes from zone C in the network contained those involved in recognition and clearance of immune complexes (FCGR2A), tissue-damaging oxidative molecules (CD163), complex carbohydrate structures (MRC1) (35,36), and those that facilitate the repair and regeneration of damaged tissues such as MMP12 and SPP1 (37). This observation was reminiscent of a recently documented role of Treg cells in tissue repair after injury (38).…”

Section: Interactions Between Treg Cell and Teff Cell Genesmentioning

confidence: 86%

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Hua

Davis

Hill

et al. 2015

The Journal of Immunology

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Regulatory T (Treg) cells have a critical role in the control of immunity, and their diverse subpopulations may allow adaptation to different types of immune responses. In this study, we analyzed human Treg cell subpopulations in the peripheral blood by performing genome-wide expression profiling of 40 Treg cell subsets from healthy donors. We found that the human peripheral blood Treg cell population is comprised of five major genomic subgroups, represented by 16 tractable subsets with a particular cell surface phenotype. These subsets possess a range of suppressive function and cytokine secretion and can exert a genomic footprint on target effector T (Teff) cells. Correlation analysis of variability in gene expression in the subsets identified several cell surface molecules associated with Treg suppressive function, and pharmacological interrogation revealed a set of genes having causative effect. The five genomic subgroups of Treg cells imposed a preserved pattern of gene expression on Teff cells, with a varying degree of genes being suppressed or induced. Notably, there was a cluster of genes induced by Treg cells that bolstered an autoinhibitory effect in Teff cells, and this induction appears to be governed by a different set of genes than ones involved in counteracting Teff activation. Our work shows an example of exploiting the diversity within human Treg cell subpopulations to dissect Treg cell biology.

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Section: Interactions Between Treg Cell and Teff Cell Genesmentioning

confidence: 86%

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Hua

Davis

Hill

et al. 2015

The Journal of Immunology

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“…Ectodomain shedding of soluble CD163 from the cell surface of monocytic cells is believed to be the direct result of upregulated CD163 and TNF‐ α expression by macrophages 21. While TNF‐ α is fairly rapidly cleared, soluble CD163 may be a long‐lived surrogate marker for macrophage activation following tissue injury 16. Aside from the utility of sCD163 as a biomarker of inflammation, the biological function of the soluble form of CD163 is not yet well established, although some studies suggest that sCD163 retains the capacity to bind haptoglobin‐hemoglobin complexes and exert anti‐inflammatory effects 22, 23…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, histological evaluation of CD163 in brain tissue is not a practical tool for clinical prediction of ICH outcome. However, CD163 has been shown to undergo cleavage from the cell surface, resulting in a soluble form that circulates in plasma 16. Therefore, we hypothesized that this soluble form of CD163 (sCD163) may represent a promising prognostic marker for PHE expansion and functional outcome in ICH.…”

Section: Introductionmentioning

confidence: 99%

Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema

Roy-O’Reilly

Zhu

Atadja

et al. 2017

Ann Clin Transl Neurol

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ObjectivePatients with intracerebral hemorrhage (ICH) may elaborate varying degrees of perihematomal edema (PHE), requiring closer monitoring and a higher intensity of treatment. Here, we explore whether the soluble form of CD163, a scavenger receptor responsible for hemoglobin sequestration, can serve as a prognostic biomarker of PHE development and poor outcome after ICH.MethodsOur study cohort was comprised of 51 primary age‐ and sex‐matched ICH patients with moderate‐sized, hypertensive deep hemorrhages. Patients were part of a prospective ICH registry cataloguing admission data along with functional outcomes. We measured sCD163 levels in serial serum and cerebrospinal fluid (CSF) samples obtained at prespecified timepoints. Descriptive statistics, including a generalized estimating equation for longitudinal data, were used to analyze sCD163 in relation to ICH outcomes.ResultsAcute serum sCD163 (<48 h postictus) was significantly elevated in ICH patients compared to both acute neurological event controls (P = <0.001) and healthy controls (P = 0.003). As predicted, acute serum sCD163 levels were significantly associated with both hematoma volume expansion (P = 0.009) and PHE expansion (P = 0.002). Further examination determined that patients with high PHE expansion had poorer modified Rankin Scale scores at discharge (P = 0.024), and circulating sCD163 levels were found to be significantly lower in patients with high‐level PHE expansion.InterpretationAcute sCD163 levels may be a useful biomarker for the acute identification of patients at risk for hematoma expansion, perihematomal edema expansion and poorer short‐term outcomes.

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“…Complexes of S100A8/S100A9 (calprotectin) are also ligands of Toll-like receptor 4 (21) and contribute to ongoing innate immune activation in inflammatory disease states. CD163 is produced by activated macrophages and elevated in inflammatory diseases (20,28), whereas both IL8 and CXCL6 are potent neutrophil chemoattractants. The reduced levels of MPO in the ANTI pigs are consistent with the reduction in these inflammatory chemokines.…”

Section: Discussionmentioning

confidence: 99%

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

Jensen

Thymann

Cilieborg

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

103

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Preterm birth, bacterial colonization, and formula feeding predispose to necrotizing enterocolitis (NEC). Antibiotics are commonly administered to prevent sepsis in preterm infants, but it is not known whether this affects intestinal immunity and NEC resistance. We hypothesized that broad-spectrum antibiotic treatment improves NEC resistance and intestinal structure, function, and immunity in neonates. Caesarean-delivered preterm pigs were fed 3 days of parenteral nutrition followed by 2 days of enteral formula. Immediately after birth, they were assigned to receive either antibiotics (oral and parenteral doses of gentamycin, ampicillin, and metronidazole, ANTI, n ϭ 11) or saline in the control group (CON, n ϭ 13), given twice daily. NEC lesions and intestinal structure, function, microbiology, and immunity markers were recorded. None of the ANTI but 85% of the CON pigs developed NEC lesions by day 5 (0/11 vs. 11/13, P Ͻ 0.05). ANTI pigs had higher intestinal villi (ϩ60%), digestive enzyme activities (ϩ53-73%), and goblet cell densities (ϩ110%) and lower myeloperoxidase (Ϫ51%) and colonic microbial density (10 5 vs. 10 10 colony-forming units, all P Ͻ 0.05). Microarray transcriptomics showed strong downregulation of genes related to inflammation and innate immune response to microbiota and marked upregulation of genes related to amino acid metabolism, in particular threonine, glucose transport systems, and cell cycle in 5-day-old ANTI pigs. In a follow-up experiment, 5 days of antibiotics prevented NEC at least until day 10. Neonatal prophylactic antibiotics effectively reduced gut bacterial load, prevented NEC, intestinal atrophy, dysfunction, and inflammation and enhanced expression of genes related to gut metabolism and immunity in preterm pigs.

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CD163 and Inflammation: Biological, Diagnostic, and Therapeutic Aspects

Abstract: The diagnostic and therapeutic properties of CD163 await further clinical studies and regulatory approval before implementation in the clinic.

Cited by 436 publications

References 123 publications

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Diverse Gene Expression in Human Regulatory T Cell Subsets Uncovers Connection between Regulatory T Cell Genes and Suppressive Function

Soluble CD163 in intracerebral hemorrhage: biomarker for perihematomal edema

Antibiotics modulate intestinal immunity and prevent necrotizing enterocolitis in preterm neonatal piglets

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