Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Leptin Promotes T Cell Autoimmunity through Modulation of the PKB/Akt/mTOR Pathway in Systemic Lupus Erythematosus (SLE) Patients.
Lourenco, Elaine V., Hahn, Bevra H., Iikuni, Noriko, Kim, Sarah J., Wong, Maida, Singh, Ram P., Grossman, Jennifer
Leptin is a pro-inflammatory (adipo)cytokine that promotes the onset and progression of organ-specific autoimmunity by facilitating pro-inflammatory immune responses. We investigated the possibility that leptin could modulate autoimmune T cell reactivity in systemic lupus erythematosus (SLE) patients, and found that the elevation of leptin in plasma from SLE patients (n=164) - as compared to matched controls (n=124)(p<0.0001) - facilitated the proliferation and release of pro-inflammatory cytokines in peripheral autoreactive SLE CD4+ T cells. These effects were abrogated if leptin was blocked by antibodies anti-leptin, anti-leptin receptor, or leptin receptor chimera. Interestingly, the effects of leptin were different on the CD4+CD25-FoxP3- effector T cells (TEff) and CD4+CD25+FoxP3+ regulatory T cells (TReg). In particular, leptin promoted the proliferation and release of pro-inflammatory cytokines in TEff and it constrained the activity of TReg, with a net result of unabated autoreactive TEff responses. These effects associated with leptin-induced differential activation of the protein kinase B (PKB)/Akt/mTOR signaling pathway in autoreactive TEff versus TReg, and this action could be reversed by pharmacologic intervention. These findings identify a new mechanism through which leptin can concomitantly promote T cell autoreactivity and inhibit immune suppression in SLE, suggesting the possibility of targeted leptin-based intervention for the control of unbalanced T cell autoimmune reactivity in the disease.
To cite this abstract, please use the following information:
Lourenco, Elaine V., Hahn, Bevra H., Iikuni, Noriko, Kim, Sarah J., Wong, Maida, Singh, Ram P., et al; Leptin Promotes T Cell Autoimmunity through Modulation of the PKB/Akt/mTOR Pathway in Systemic Lupus Erythematosus (SLE) Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :497