NKG2D receptor regulates CD4⁺T cell differentiation via interaction with dendritic cells in patients with juvenile...

NKG2D provides a costimulatory signal for activation of CD4+ T cells. We explored its role in interactions of CD4+ T cells and dendritic cells (DCs) in juvenile idiopathic arthritis (JIA) patients by using NKG2D genetically modified CD4+ T cells. We found active JIA patients had significantly higher content of CD4 + NKG2D+ T cells than healthy controls. Expression of NKG2D on CD4+ T cells, and MICA and MICB on DCs were significantly greater in articular JIA than systemic JIA. 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. NKG2D decreased IL-10 and increased CD83, MICA, and MICB of DCs in JIA and controls. So NKG2D regulates differentiation of CD4+ T cells directly and the maturation of DCs indirectly.