RGD Reference Report - Critical role of IL-21 in modulating TH17 and regulatory T cells in Behcet disease. - Rat Genome Database

Send us a Message

Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Critical role of IL-21 in modulating TH17 and regulatory T cells in Behcet disease.

Authors: Geri, G  Terrier, B  Rosenzwajg, M  Wechsler, B  Touzot, M  Seilhean, D  Tran, TA  Bodaghi, B  Musset, L  Soumelis, V  Klatzmann, D  Cacoub, P  Saadoun, D 
Citation: Geri G, etal., J Allergy Clin Immunol. 2011 Sep;128(3):655-64. Epub 2011 Jul 2.
RGD ID: 6892926
Pubmed: PMID:21724243   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jaci.2011.05.029   (Journal Full-text)

BACKGROUND: Behcet disease (BD) is a chronic systemic inflammatory disorder of unknown etiology. OBJECTIVE: To determine the nature of T cells driving inflammatory lesions in BD. METHODS: T cell homeostasis and cytokines production were analyzed in peripheral blood and brain inflammatory lesions from 45 adult patients with BD (active and untreated BD [n = 25] and patients in remission [n = 20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry, and immunofluorescence analysis. RESULTS: We found a marked increase in T(H)17 cells and a decrease in the frequency of CD4(+) forkhead box P3(+) regulatory T cells (Tregs) in peripheral blood that were induced by IL-21 production and that correlate with BD activity. The addition of serum from patients with active BD in a sorted CD4(+) T cells culture of healthy donors induced a significant and dose-dependent production of IL-17A and a decrease in forkhead box P3 expression. We demonstrated the presence of IL-21- and IL-17A-producing T cells within the cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral blood vessels from patients with active BD and central nervous system involvement. The stimulation of CD4(+) T cells with IL-21 increased T(H)17 and T(H)1 differentiation and decreased the frequency of Treg cells. Conversely, IL-21 blockade with an IL-21R-Fc restored the T(H)17 and Treg homeostasis in patients with BD. CONCLUSION: We provided here the first evidence of the critical role of IL-21 in driving inflammatory lesions in BD by promoting T(H)17 effectors and suppressing Treg cells. IL-21 represents a promising target for novel therapy in BD.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Behcet's disease  IMP 6892926 RGD 
Behcet's disease  ISOIL21R (Homo sapiens)6892926; 6892926 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il21r  (interleukin 21 receptor)

Genes (Mus musculus)
Il21r  (interleukin 21 receptor)

Genes (Homo sapiens)
IL21R  (interleukin 21 receptor)

Additional Information