NKG2D receptor regulates CD4 + T cell differentiation via interaction
with dendritic cells in patients with juvenile idiopathic arthritis
Abstract
Objectives: To explore roles of NKG2D in interactions of CD4
+ T cells and dendritic cells (DCs) in juvenile
idiopathic arthritis (JIA) patients Methods: Peripheral blood
from active JIA patients and healthy controls were used for flow
cytometry assessments of NKG2D +CD4
+ T cells and expressions of MICA and MICB on DCs.
NKG2D genetically modified CD4 + T cells resulted from
transfection with lentiviral vectors harboring NKG2D and NKG2D siRNA.
ELISA measured supernatant cytokines in co-cultured CD4
+ T cells and DCs. CD4 + T cell
subgroups, MICA and MICB expression on DCs was determined by flow
cytometry and transcription factors by real-time PCR. Results:
All JIA patients had significantly higher content of CD4
+NKG2D + T cells compared to healthy
controls (P < 0.01). Expression of NKG2D on CD4
+ T cells, and MICA and MICB on DCs were significantly
greater in articular JIA than systemic JIA (P < 0.05). NKG2D
induced IL-12 and suppressed IL-10 and TGF-β from CD4
+ T cells, increased IFN-γ + CD4+ T
and IL-17 + CD4 + T cells, RORc and
T-bet, but reduced CD25 + Foxp3 +
CD4 + T cells, IL-4 + CD4
+ T cells, Foxp3, and GATA3 in JIA patients
(P<0.05). NKG2D increased IL-12 and T-bet by CD4
+ T cells in healthy controls (P<0.05).
NKG2D decreased IL-10 and increased CD83, MICA, and MICB of DCs via
interaction with CD4 + T cells in JIA and control
patients (P<0.05). Conclusions: NKG2D regulates
differentiation of CD4 + T cells directly and the
maturation of DCs indirectly. Targeting NKG2D may be a potential therapy
for JIA.