Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Leptin Modulates Apoptosis of Autoimmune T Cells in Systemic Lupus Erythematosus.
Amarilyo1, Gil, Iikuni2, Noriko, Hahn3, Bevra H., La Cava4, Antonio
In systemic lupus erythematosus (SLE), the abnormal clearance of dead cells leads to the availability and accumulation of self-antigens that can facilitate the initiation and maintenance of T cell-driven autoimmune responses. Leptin is an adipokine that controls metabolism and pro-inflammatory immune responses, and is significantly increased in patients and mice with SLE. Purpose of this study was to study the influence of leptin on apoptosis in SLE.
Thymocytes from (NZB x NZW)F1 (BWF1) lupus-prone mice were incubated with dexamethasone (that promotes apoptosis) in the presence or not of leptin and compared with their parental strains (NZB and NZW mice) for the induction of apoptosis (measured by TUNEL assay). Additional controls included thymocytes from non autoimmune mice. The expression of the anti-apoptotic molecule bcl-2 in CD4 T cells was evaluated in parallel by flow cytometry. To study the effects of leptin on apoptosis in autoreactive CD4 T cells, ovalbumin (OVA) T-cell receptor transgenic DO11.10 mice were immunized with OVA and then divided into two groups: one receiving leptin and one serving as control (receiving vehicle). Peripheral OVA-specific autoreactive T cells sorted by tetramer staining were co-stained for BrDU, annexin V and bcl-2. Concomitantly, proliferation and apoptosis of peripheral autoreactive cells in BWF1 lupus mice immunized with two different anti-DNA Ig-derived epitopes and treated or not with leptin was investigated.
Leptin inhibted T cell apoptosis in BWF1 lupus mice as compared to the parental NZB and NZW mice (P<0.03 for both) and to the non-autoimmune animals (P<0.01). This inhibition of apoptosis by leptin associated with the upregulation of the anti-apoptotic molecule bcl-2 (P<0.009), both in thymocytes and in peripheral T cells. Interestingly, administration of leptin facilitated the survival and proliferation of peripheral T cells autoreactive to anti-DNA Ig-derived epitopes in BWF1 lupus mice, as shown in flow cytometry and proliferation assays. Similarly, in OVA-transgenic DO11.10 mice, leptin treatment was associated with inhibition of apoptosis and the induction of bcl-2 in peripheral OVA-specific CD4 T cells, and also with an increased proliferation of the autoreactive T cells.
Leptin facilitates the survival and proliferation of autoreactive T-cells through a leptin-dependent upregulation of bcl-2. This newly described role of leptin in the facilitation of autoreactive T cell activity in SLE may have implications for new targeted therapeutic approaches in the disease.
To cite this abstract, please use the following information:
Amarilyo, Gil, Iikuni, Noriko, Hahn, Bevra H., La Cava, Antonio; Leptin Modulates Apoptosis of Autoimmune T Cells in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :2361