2014
DOI: 10.1084/jem.20130301
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Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids

Abstract: Inflammatory T helper 17 cells in humans are distinguished by selective expression of MDR1 and are enriched in the gut of patients with Crohn’s disease.

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Cited by 395 publications
(439 citation statements)
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“…demonstrated, in CD patients, a MDR1 enrichment within Th1.17 that resist to GC treatment. 61 On the contrary, MDR1 loss of function was identified in a subset of patients with an aggressive form of ileal CD. 78 Therefore, MDR1 role is dual in this pathology.…”
Section: Introductionmentioning
confidence: 99%
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“…demonstrated, in CD patients, a MDR1 enrichment within Th1.17 that resist to GC treatment. 61 On the contrary, MDR1 loss of function was identified in a subset of patients with an aggressive form of ileal CD. 78 Therefore, MDR1 role is dual in this pathology.…”
Section: Introductionmentioning
confidence: 99%
“…In healthy subjects, among CD4 + memory T cells, MDR1 delineates a subset of effector T cells (Teff) mainly composed of Th1.17 also called pathogenic Th17. 61 Moreover, our team recently characterized, in human, the CD73 + Teff population that is particularly enriched in Th1.17 and expressed higher MDR1 levels than their CD73 neg counterpart. 62 A recent study also suggests that MDR1 is also selectively expressed by Teff bearing the lectin-like receptor CD161.…”
Section: Introductionmentioning
confidence: 99%
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“…Increasing evidence supports the concept of a SR Th17 phenotype, and their adoptive transfer, or the overexpression of their canonical transcription factor retinoid-related orphan receptor (ROR)-γt, has been shown to induce SR disease in a murine model of asthma (12,13). In humans, glucocorticoid-resistant Th17 cells express the multidrug resistance type 1 protein, which is inhibited by cyclosporine A (CsA) (14), and historically CsA was one of the first drugs used to successfully rescue SR diseases (1). We therefore hypothesized that CsA would selectively inhibit human Th17 cells.…”
mentioning
confidence: 99%
“…P-glycoprotein, for example, is under the influence of PXR, FXR, NFκB and AP-1 pathways (Miller, 2010), but examination of co-regulated transcripts using pathway analysis tools may help determine the specific pathway that is active (Krämer et al, 2014). It has been demonstrated that microbial-derived compounds including indole metabolites can function as PXR ligands (Venkatesh et al, 2014) which have functions in other cell types such is the case with P-glycoprotein expressed in phagocytes and T cells (Ramesh et al, 2014;Cory et al, 2016).…”
Section: Alternative Alterations To Absorptionmentioning
confidence: 99%