Abstract
In systemic lupus erythematosus (SLE), the availability of self-antigen promotes and fuels self-reactive immune responses. Apoptotic cells represent a major source of self-antigens, and an impairment of the removal of apoptotic material containing self-antigen can contribute to the development of autoimmunity. To address whether the adipocytokine leptin - which favors autoimmune responses through little understood mechanisms - could modulate the handling of apoptotic cells in SLE, we evaluated the ability of leptin to modulate the capacity of macrophages to phagocytose apoptotic bodies in (NZB×NZW)F1 lupus mice. It was found that leptin promoted phagocytosis of apoptotic cells by macrophages by modulating cAMP levels in macrophages. This finding associated with an increased availability of antigen that favored the development of T cell responses to apoptotic-derived antigen. As leptin promotes macrophage phagocytosis of apoptotic bodies in SLE and subsequent availability of apoptotic-derived antigen to T cells, an inhibition of this process via leptin blockade might have a therapeutic potential in SLE.
Highlights
Apoptotic cell death and subsequent clearance of apoptotic bodies have an important role in the maintenance of immune tolerance
We focused on the fact that the clearance of apoptotic cells by macrophages is critical for the control of tissue homeostasis, and that an impairment in the uptake of apoptotic cells can lead to the generation of autoantibodies to nuclear antigens and the activation ofimmune cells. [11,12] We found that leptin promoted availability of apoptotic cell-derived antigen in lupus mice which, in turn, favored expansion of antigen-reactive T cells
Leptin promotes lupus macrophage phagocytosis in vitro In systemic lupus erythematosus (SLE), the impaired clearance of apoptotic cells causes an accumulation of cellular material that contains self-antigen. [1,2,14] To test a possible role of leptin in this process, we co-cultured - in the presence of scalar doses of leptin - purified macrophages derived from NZB/W lupus mice together with CFSE-labeled apoptotic cells
Summary
Apoptotic cell death and subsequent clearance of apoptotic bodies have an important role in the maintenance of immune tolerance. Phagocytosis in vitro Three days after thioglycolate injection, peritoneal macrophages were collected from abdominal cavities and co-cultured in serumfree HL-1 medium (Lonza, Anaheim, CA) with CFSE-labeled apoptotic Jurkat T cells (16107 cells) in the presence of scalar doses of leptin.
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