Maintenance of autoantibody production in pristane-induced murine lupus

Han, Sung‐Sik; Zhuang, Haoyang; Xu, Yuan; Lee, Pui Y.; Li, Yang; Wilson, Judy R.; Vidal, Osvaldo; Choi, Hong Seok; Sun, Yu; Yang, Lijun; Reeves, Westley H.

doi:10.1186/s13075-015-0886-9

Cited by 20 publications

(17 citation statements)

References 55 publications

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“…The measurement of autoantibodies (autoAb) showed an increase in total IgG in pristane-treated WT mice compared with mock-treated WT controls (Fig. S2A), similarly to what has been reported by others (8). Interestingly, the comparison between pristane-treated WT mice and syngeneic leptin-deficient ob/ob mice also treated with pristane revealed an increase in IgG levels in WT mice but no change in leptin-deficient ob/ob mice (Fig.…”

Section: Resultssupporting

confidence: 69%

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Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Lourenço

Liu

Matarese

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptinsufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F 1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.systemic lupus erythematosus | leptin | autoimmunity | immune regulation | animal models

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Section: Resultssupporting

confidence: 69%

“…At 8 wk of age, mice received one i.p. injection of 500 μL pristane (Sigma-Aldrich) or saline (8). Blood was collected before pristane injection and after 1, 3, 5, and 7 mo.…”

Section: Methodsmentioning

confidence: 99%

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Lourenço

Liu

Matarese

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Pristane injection induces a polyclonal hypergammaglobulinemia associated with an enrichment of antibody producing cells and high autoantibody titers raised against nuclear antigens (mainly ribonucleoproteins in the C57BL/6 genetic background) leading to the chronic autoimmune phenotype 16 , 31 . The autoantibody titers are maintained by the continuous source of necrotic/apoptotic ligands driving cytokine production and B cell differentiation 18 , 32 . We confirmed these data by detecting a significant hypergammaglobulinemia and a significant increase in proportion of antibody producing cells (CD19 + CD138 + ) and in anti-RNP specific IgG autoantibody titers in pristane-injected C57BL/6 mice (Figs S2 and 3 ).…”

Section: Results and Discusssionmentioning

confidence: 99%

Basophils contribute to pristane-induced Lupus-like nephritis model

Dema

Lamri

Pellefigues

et al. 2017

Sci Rep

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Lupus nephritis (LN), one of the most severe outcomes of systemic lupus erythematosus (SLE), is initiated by glomerular deposition of immune-complexes leading to an inflammatory response and kidney failure. Autoantibodies to nuclear antigens and autoreactive B and T cells are central in SLE pathogenesis. Immune mechanisms amplifying this autoantibody production drive flares of the disease. We previously showed that basophils were contributing to LN development in a spontaneous lupus-like mouse model (constitutive Lyn −/− mice) and in SLE subjects through their activation and migration to secondary lymphoid organs (SLOs) where they amplify autoantibody production. In order to study the basophil-specific mechanisms by which these cells contribute to LN development, we needed to validate their involvement in a genetically independent SLE-like mouse model. Pristane, when injected to non-lupus-prone mouse strains, induces a LN-like disease. In this inducible model, basophils were activated and accumulated in SLOs to promote autoantibody production. Basophil depletion by two distinct approaches dampened LN-like disease, demonstrating their contribution to the pristane-induced LN model. These results enable further studies to decipher molecular mechanisms by which basophils contribute to lupus progression.

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“…Pristane has been widely used to induce a lupus-like syndrome in multiple mouse strains 14 15 . The leukocyte ligand Psgl-1 may promote inflammation in lupus by mediating leukocyte tissue infiltration through interaction with selectins.…”

Section: Resultsmentioning

confidence: 99%

Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus

Wang

Knight

Hodgin

et al. 2016

Sci Rep

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Systemic lupus erythematosus (SLE) is associated with an elevated risk of vascular complications, including premature stroke. Therapies targeting leukocyte recruitment may be beneficial in reducing vascular complications associated with SLE. Lupus was induced in female wild-type (WT) and P-selectin glycoprotein ligand-1 deficient (Psgl-1−/−) mice with pristane. Stroke was induced following photochemical injury to the middle cerebral artery (MCA). Stroke size was increased in pristane-treated WT mice compared to non-pristane-treated WT controls. However, stroke size was not increased in pristane-treated Psgl-1−/− mice compared to controls, despite evidence of increased nephritis in Psgl-1−/− mice. Pristane-treated WT mice showed elevated anti-dsDNA, anti-snRNP, CXCL1, and MCP-1 levels compared to untreated mice; however levels of anti-snRNP, MCP-1, and CXCL1 were reduced in pristane-treated Psgl-1−/− mice compared to pristane-treated WT mice. Infiltration of neutrophils and macrophages at the cerebral infarction site were reduced in pristane-treated Psgl-1−/− mice compared to pristane-treated WT mice. In conclusion, the increase in stroke size associated with lupus is prevented by Psgl-1 deficiency while nephritis is exacerbated. Therapies targeting Psgl-1 may be useful in the management of SLE patients at high risk of acute vascular complications although elucidation of downstream pathways will be necessary to identify targets that do not promote nephritis.

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Maintenance of autoantibody production in pristane-induced murine lupus

Cited by 20 publications

References 55 publications

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Basophils contribute to pristane-induced Lupus-like nephritis model

Psgl-1 Deficiency is Protective against Stroke in a Murine Model of Lupus

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