TY - JOUR
T1 - A Key Role of Leptin in the Control of Regulatory T Cell Proliferation
AU - De Rosa, Veronica
AU - Procaccini, Claudio
AU - Calì, Gaetano
AU - Pirozzi, Giuseppe
AU - Fontana, Silvia
AU - Zappacosta, Serafino
AU - La Cava, Antonio
AU - Matarese, Giuseppe
PY - 2007/2/23
Y1 - 2007/2/23
N2 - We report here that leptin can act as a negative signal for the proliferation of human naturally occurring Foxp3
+CD4
+CD25
+ regulatory T (T
reg) cells. Freshly isolated T
reg cells produced leptin and expressed high amounts of leptin receptor (ObR). In vitro neutralization with leptin monoclonal antibody (mAb), during anti-CD3 and anti-CD28 stimulation, resulted in T
reg cell proliferation, which was interleukin-2 (IL-2) dependent. T
reg cells that proliferated in the presence of leptin mAb had increased expression of Foxp3 and remained suppressive. The phenomena appeared secondary to leptin signaling via ObR and, importantly, leptin neutralization reversed the anergic state of the T
reg cells, as indicated by downmodulation of the cyclin-dependent kinase inhibitor p27 (p27
kip1) and the phosphorylation of the extracellular-related kinases 1 (ERK1) and ERK2. Together with the finding of enhanced proliferation of T
reg cells observed in leptin- and ObR-deficient mice, these results suggest a potential for therapeutic interventions in immune and autoimmune diseases.
AB - We report here that leptin can act as a negative signal for the proliferation of human naturally occurring Foxp3
+CD4
+CD25
+ regulatory T (T
reg) cells. Freshly isolated T
reg cells produced leptin and expressed high amounts of leptin receptor (ObR). In vitro neutralization with leptin monoclonal antibody (mAb), during anti-CD3 and anti-CD28 stimulation, resulted in T
reg cell proliferation, which was interleukin-2 (IL-2) dependent. T
reg cells that proliferated in the presence of leptin mAb had increased expression of Foxp3 and remained suppressive. The phenomena appeared secondary to leptin signaling via ObR and, importantly, leptin neutralization reversed the anergic state of the T
reg cells, as indicated by downmodulation of the cyclin-dependent kinase inhibitor p27 (p27
kip1) and the phosphorylation of the extracellular-related kinases 1 (ERK1) and ERK2. Together with the finding of enhanced proliferation of T
reg cells observed in leptin- and ObR-deficient mice, these results suggest a potential for therapeutic interventions in immune and autoimmune diseases.
KW - CELLIMMUNO
KW - HUMDISEASE
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U2 - 10.1016/j.immuni.2007.01.011
DO - 10.1016/j.immuni.2007.01.011
M3 - Article
C2 - 17307705
AN - SCOPUS:33847312289
VL - 26
SP - 241
EP - 255
JO - Immunity
JF - Immunity
SN - 1074-7613
IS - 2
ER -