Editors' ChoiceImmunology

Lupus and leptin

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Science Signaling  27 Sep 2016:
Vol. 9, Issue 447, pp. ec223
DOI: 10.1126/scisignal.aak9751

Systemic lupus erythematosus (SLE) is a poorly understood autoimmune disorder that is thought to be influenced by multiple interacting factors, including sex hormones and the environment. In a study with mouse models of SLE, Lourenço et al. found that progression of the disease may be partially mediated by the “satiety hormone” leptin. In addition to being involved in regulating appetite, leptin acts as a proinflammatory cytokine, and previous studies showed increased serum leptin concentrations in patients with SLE. The hydrocarbon oil pristane, which induces SLE-like symptoms in mice, increased the serum concentration of leptin in wild-type mice compared with that in untreated mice. Whereas pristane increased the serum concentrations of SLE-associated autoantibodies against chromatin, ribonucleoprotein (RNP), single-stranded DNA (ssDNA), and double-stranded DNA (dsDNA) in wild-type mice, leptin-deficient (ob/ob) mice were unaffected. Additionally, pristane induced proliferative glomerulonephritis, an SLE-associated kidney disease, in wild-type but not leptin-deficient mice. Circulating leptin concentrations increased with age in an SLE-prone strain of mice (NZB/W), and treating these mice with anti–leptin antibodies increased their lifespan. Both the pristane-induced and spontaneous models of SLE showed effects of leptin on immune cell composition. Leptin-deficient ob/ob mice had increased numbers of CD4+CD25+ T regulatory (Treg) cells compared with wild type mice, both with and without pristane treatment, and the anti–leptin antibody increased the number of Treg cells in nephritic NZB/W mice. Leptin prevented the transforming growth factor–β (TGF-β)–induced conversion of CD4+CD25 T cells into Treg cells in vitro, suggesting that leptin could function in SLE to inhibit the generation of these suppressor cells. The prevalence of SLE is higher among women than among men, and women tend to have higher concentrations of leptin. Thus, this hormone, which links metabolism and immunity, could be a therapeutic target for the treatment of SLE.

E. V. Lourenço, A. Liu, G. Matarese, A. La Cava, Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation. Proc. Nat. Acad. Sci. U.S.A. 113, 10637–10642 (2016). [PubMed]

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