RT Journal Article
SR Electronic
T1 Akt-Dependent Enhanced Migratory Capacity of Th17 Cells from Children with Lupus Nephritis
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 4895
OP 4903
DO 10.4049/jimmunol.1400044
VO 193
IS 10
A1 Kshirsagar, Sudhir
A1 Riedl, Magdalena
A1 Billing, Heiko
A1 Tönshoff, Burkhard
A1 Thangavadivel, Shanmugapriya
A1 Steuber, Christian
A1 Staude, Hagen
A1 Wechselberger, Gottfried
A1 Edelbauer, Monika
YR 2014
UL http://www.jimmunol.org/content/193/10/4895.abstract
AB Th17 cells infiltrate the kidneys of patients with lupus nephritis (LN) and are critical for the pathogenesis of this disease. In this study, we show that enhanced activity of Stat3 in CD4+CD45RA−Foxp3− and Foxp3low effector T cells from children with LN correlates with increased frequencies of IL-17–producing cells within these T cell populations. The levels of retinoic acid-related orphan receptor c and IL-17 mRNA are significantly higher in PBMCs from children with LN than in those from controls. Mammalian target of rapamycin inhibition by rapamycin reduces both Stat3 activation in effector T cells and the frequency of IL-17–producing T cells in lupus patients. Complement factor C5a slightly increases the expression of IL-17 and induces activation of Akt in anti-CD3–activated lupus effector T cells. Th17 cells from children with LN exhibit high Akt activity and enhanced migratory capacity. Inhibition of the Akt signaling pathway significantly decreases Th17 cell migration. These findings indicate that the Akt signaling pathway plays a significant role in the migratory activity of Th17 cells from children with LN and suggest that therapeutic modulation of the Akt activity may inhibit Th17 cell trafficking to sites of inflammation and thus suppress chronic inflammatory processes in children with LN.