ArticleThe Journal of experimental medicine2014
Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04096222 (Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients), which is not on this map. Cited by 266 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Comparative Analysis of the Th17 Cellular Response in Active and Inactive Pemphigus Vulgaris Patients
Who cites it
266 citing papers in PubMed, 2 syntheses or guidelines pooled it, 439 citations in OpenAlex.
- Corticosteroid monotherapy for the management of Takayasu arteritis-a systematic review and meta-analysis.Rheumatology international · 2021Pooled it
- Meta-analysis of transcriptomic variation in T-cell populations reveals both variable and consistent signatures of gene expression and splicing.RNA (New York, N.Y.) · 2020Pooled it
- IL-17A is a pertinent therapeutic target for moderate-to-severe hidradenitis suppurativa: Combined results from a pre-clinical and phase II proof-of-concept study.Experimental dermatology · 2022Trial
- Low-dose IL-2 improved clinical symptoms by restoring reduced regulatory T cells in patients with refractory rheumatoid arthritis: A randomized controlled trial.Frontiers in immunology · 2022Trial
- Reconstitution of immune cell populations in multiple sclerosis patients after autologous stem cell transplantation.Clinical and experimental immunology · 2017Trial
- Mapping the Impact of Janus Kinase Inhibitors at a Cellular Resolution in Inflammatory Bowel Disease.Cellular and molecular gastroenterology and hepatology · 2026Review
- Systemic immune activation in hereditary cancer predisposition syndromes: a cross-sectional study.BMC medicine · 2026Article
- A cell-intrinsic glucocorticoid biosynthesis and sensing circuit maintains a homeostatic Th17 cell state.Immunity · 2026Article
- Refined single-cell profiling captures a CCR5EBioMedicine · 2026Article
- Multicellular crosstalk in neutrophilic asthma: unraveling the pathogenic web of steroid resistance and emerging precision therapies.Journal of translational medicine · 2026Review
- HLA-DRRespiratory research · 2026Article
- Context-specific roles for IL-17 in tuberculosis.PLoS pathogens · 2026Review
- IL-23 and monocyte interactions redirect human Th17.1 cells to an IL-17AFrontiers in immunology · 2026Article
- Targeting pathogenic Th17.1 cells via JAK-STAT3 pathway: A novel approach with tofacitinib for refractory myasthenia gravis.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Metabolic Adaptation of CD8⁺ T Cells Limits the Efficacy of Fatty Acid Oxidation Inhibition in Type 1 Diabetes.International journal of biological sciences · 2026Article
- Pro-Inflammatory c-MetAnnals of neurology · 2026Article
- Differential Transcriptomic Features of Peripheral Blood Mononuclear Cells in Pulmonary Sarcoidosis with and Without Extrapulmonary Lesions in an East Asian Population.Biomedicines · 2025Article
- Blood and tissue correlates of steroid non-response in checkpoint inhibition-induced immune-related adverse events.Communications medicine · 2025Article
- T-cell and autoantibody profiling for primary immune regulatory disorders.The Journal of allergy and clinical immunology · 2025Article
- Advances in mechanistic investigation and treatment of steroid-refractory ICI-induced liver injury.Clinical and experimental medicine · 2025Review
206 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
IL-17A-expressing CD4(+) T cells (Th17 cells) are generally regarded as key effectors of autoimmune inflammation. However, not all Th17 cells are pro-inflammatory. Pathogenic Th17 cells that induce autoimmunity in mice are distinguished from nonpathogenic Th17 cells by a unique transcriptional signature, including high Il23r expression, and these cells require Il23r for their inflammatory function. In contrast, defining features of human pro-inflammatory Th17 cells are unknown. We show that pro-inflammatory human Th17 cells are restricted to a subset of CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) cells that transiently express c-Kit and stably express P-glycoprotein (P-gp)/multi-drug resistance type 1 (MDR1). In contrast to MDR1(-) Th1 or Th17 cells, MDR1(+) Th17 cells produce both Th17 (IL-17A, IL-17F, and IL-22) and Th1 (IFN-γ) cytokines upon TCR stimulation and do not express IL-10 or other anti-inflammatory molecules. These cells also display a transcriptional signature akin to pathogenic mouse Th17 cells and show heightened functional responses to IL-23 stimulation. In vivo, MDR1(+) Th17 cells are enriched and activated in the gut of Crohn's disease patients. Furthermore, MDR1(+) Th17 cells are refractory to several glucocorticoids used to treat clinical autoimmune disease. Thus, MDR1(+) Th17 cells may be important mediators of chronic inflammation, particularly in clinical settings of steroid resistant inflammatory disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.