574 - Leptin Impinges on the Clearance of Autoimmune T Cells in Murine Lupus

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Gil Amarilyo, University of California, Los Angeles, Los Angeles, CA, Noriko Iikuni, UCLA, CA, Bevra H. Hahn, UCLA David Geffen School of Medicine, Los Angeles, CA and Antonio La Cava, Univ of California Los Angeles, Los Angeles, CA
Presentation Number: 574

Background/Purpose: Leptin, a pro-inflammatory adipokine, is elevated in systemic lupus erythematosus ( SLE) patients and accelerates proteinuria in lupus-prone (NZB x NZW)F1 (BWF1) mice. However, the role of leptin in the induction and maintenance of autoimmune response in SLE has been only partially explored. Since the availability of self antigen through apoptotic material has been shown to play a key role in the autoimmune pathogenesis of SLE, we investigated whether leptin can influence phagocytosis and clearance of apoptotic T cells in SLE.

Methods: We investigated the ability of BWF1 mice to phagocyte apoptotic cells in vivo. Labeled apoptotic T cells were injected into the intraperitoneal cavity of BWF1 mice pretreated with thioglycolate for the activation of local macrophages. A group of recipient mice received leptin, another group received leptin blockers, and a third group that received vehicle served as control. Macrophages were isolated from the peritoneal fluid and the ingestion of apoptotic cells by macrophages was evaluated via costaining in flow cytometry and confocal microscopy. Parallel in vitro experiments using macrophages of thyoglycolate-treated BWF1 mice incubated in vitro with labeled apoptotic T cells in the presence or not of scalar doses of leptin were also performed.

Results: In vitro and in vivo experiments showed that leptin facilitated the phagocytic uptake of apoptotic cells by inflammatory macrophages in BWF1 lupus mice, thus providing an increased availability of autoantigen (uptake of apoptotic cells in the peritoneal macrophages was 2.6± 2.1% versus 13.4 ± 3.2% in the no leptin vs leptin-treated, P<0.02). Leptin treatment also modulated apoptotic cell clearance, possibly contributing to the maintenance of the autoimmune process (P<0.03 in the comparison between leptin treated mice versus controls).

Conclusion: Leptin modulates phagocytosis and clearance of apoptotic cells in lupus-prone BWF1 mice. Ongoing experiments are exploring the possibility that a differential role of leptin in young mice vs old animals could lead to excess free autoantigen that would favor the development of humoral immune responses to self antigens in an earlier stage. Later in life, the increased phagocytosis of apoptotic cells could favor self-antigen availability to the adaptive immune system, and thus the perpetuation of autoimmunity.

Keywords: apoptosis and phagocytosis

Disclosure: G. Amarilyo, None; N. Iikuni, None; B. H. Hahn, None; A. La Cava, None.