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

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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

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL21RHumanBehcet's disease  IMP  RGD 
Il21rRatBehcet's disease  ISOIL21R (Homo sapiens) RGD 
Il21rMouseBehcet's disease  ISOIL21R (Homo sapiens) 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