Amarilyo Gil, Iikuni Noriko, Liu Aijing, Matarese Giuseppe, La Cava Antonio
University of California Los Angeles, California, Los Angeles, United States of America.
Università di Salerno, Baronissi, Italy; IRCCS MultiMedica, Milan, Italy.
PLoS One. 2014 Nov 17;9(11):e112826. doi: 10.1371/journal.pone.0112826. eCollection 2014.
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.
在系统性红斑狼疮（SLE）中，自身抗原的可及性会促进并加剧自身反应性免疫应答。凋亡细胞是自身抗原的主要来源，而清除含自身抗原的凋亡物质功能受损会促使自身免疫性疾病的发展。为了探究脂肪细胞因子瘦素（其通过尚不明确的机制促进自身免疫反应）是否能调节SLE中凋亡细胞的处理过程，我们评估了瘦素调节（NZB×NZW）F1狼疮小鼠巨噬细胞吞噬凋亡小体能力的作用。研究发现，瘦素通过调节巨噬细胞中的cAMP水平来促进巨噬细胞对凋亡细胞的吞噬作用。这一发现与抗原可及性增加相关，而抗原可及性增加有利于T细胞对凋亡衍生抗原产生应答。由于瘦素可促进SLE中巨噬细胞对凋亡小体的吞噬作用以及随后凋亡衍生抗原向T细胞的递呈，通过阻断瘦素抑制这一过程可能对SLE具有治疗潜力。
