Leptin enhances availability of apoptotic cell-derived self-antigen in systemic lupus erythematosus.
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.
University of California Los Angeles, California, Los Angeles, United States of America.
Gil
G
Amarilyo
University of California Los Angeles, California, Los Angeles, United States of America.
Noriko
N
Iikuni
University of California Los Angeles, California, Los Angeles, United States of America.
Aijing
A
Liu
Università di Salerno, Baronissi, Italy; IRCCS MultiMedica, Milan, Italy.
Giuseppe
G
Matarese
University of California Los Angeles, California, Los Angeles, United States of America.
Antonio
A
La Cava
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D002460:Cell Line; D000242:Cyclic AMP; D004195:Disease Models, Animal; D005260:Female; D020738:Leptin / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010587:Phagocytosis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D001324:Autoantigens; D020738:Leptin; D000242:Cyclic AMP