Activation of the receptor NKG2D leads to production of Th17 cytokines in CD4+ T cells of patients with Crohn's disease.
Gastroenterology
; 141(1): 217-26, 226.e1-2, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21600899
ABSTRACT
BACKGROUND & AIMS:
The natural killer group 2 member D (NKG2D) is a stimulatory receptor expressed on a subset of mucosal and peripheral CD4+ T cells in patients with Crohn's disease (CD) and other inflammatory diseases. Ligand activation of NKG2D in patients induces CD4+ T cells to release T-helper (Th) 1 cytokines and become cytotoxic. We investigated the Th17 cytokines produced by T cells that express NKG2D in blood and intestinal mucosa samples from patients with CD.METHODS:
We isolated CD4+ T cells from peripheral blood and lamina propria samples of patients with CD or ulcerative colitis (UC) and healthy individuals (controls). We analyzed the phenotype and functions of the CD4+NKG2D+ T cells and the cytokines they produce in response to NKG2D stimulation.RESULTS:
In patients with CD, CD4+ T cells that express NKG2D produced high levels of interleukin (IL)-17 and IL-22 and expressed high levels of CCR6, the IL-23 receptor, CD161, and RORC (a transcription factor that regulates expression of Th17 cytokines). CD4+ T cells that produced IL-17 expressed high levels of NKG2D and CD161. Costimulation of NKG2D and the T-cell receptor (TCR) significantly increased production of IL-17 and tumor necrosis factor α by CD4+ T cells, compared with activation of only the TCR. CD4+NKG2D+ T cells also responded to Th17 polarization.CONCLUSIONS:
NKG2D is a functional marker of CD4+ T cells that produce IL-17 in patients with CD, via costimulation of the TCR and NKG2D. Reagents developed to block NKG2D might reduce gastrointestinal inflammation in patients with CD.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Colite Ulcerativa
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Doença de Crohn
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Citocinas
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Mediadores da Inflamação
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Subfamília K de Receptores Semelhantes a Lectina de Células NK
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Células Th17
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Mucosa Intestinal
Tipo de estudo:
Observational_studies
Limite:
Adolescent
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Adult
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Animals
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Female
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Humans
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Male
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Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article