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Abstract Number: 1032

Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation

Weiwei Chen 1 and Lingyun Sun1, 1Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China (People's Republic)

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: lipocalin2, lupus nephritis and th1

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Session Information

Date: Monday, November 11, 2019

Session Title: SLE – Etiology & Pathogenesis Poster I

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Kidney involvement is a major concern in systemic lupus erythematosus (SLE). Lipocalin-2 (LCN2) has been indicated as a potential marker of the presence and severity of lupus nephritis (LN), but the role of increased LCN2 in LN and the underlying molecular mechanisms remain unclear.

Methods: LCN2 expression in naïve CD4+ T cells of SLE patients was evaluated by real-time PCR (RT-PCR). LCN2 expression in renal biopsy samples from patients with lupus nephritis was detected by immunohistochemical staining. To investigate the production of LCN2 in lupus mice during progression of LN, LCN2 expression in PBMCs and naïve CD4+ T cells were measured by RT-PCR, mRNA and protein levels of LCN2 in kidneys were measured by qPCR and western blot respectively at different stages of disease. To investigate whether increased LCN2 levels contribute to the development of LN, the MRL/lpr mice received intraperitoneal injection of anti-LCN2 antibody or recombinant LCN2. Pristane was injected to induce lupus in WT and LCN2-/- mice. At the end of the experiment, the renal pathology, proteinuria, spleen index were evaluated. The frequency of T lymphocyte subpopulations in spleen, lymph node and kidney was analyzed by flow cytometry. To further investigate whether LCN2 regulates Th1 differentiation, MACS-sorted WT and LCN2-/- naïve CD4+ T cells were differentiated into Th1 cells under specific skewing condition.

Results: Here we report that the levels of LCN2 in peripheral blood and renal tissue are highly increased in LN patients and mouse models. Elevated LCN2 in CD4+ T cells promote IFN-γ overexpression through upregulating STAT4 phosphorylation. Both genetic depletion of LCN2 in pristane-induced mice or inhibition of LCN2 by injection of anti-LCN2 antibody in MRL/lpr mice greatly improve nephritis. The frequency of splenic or renal Th1 cells reduces in proportion to LN disease acitivity. Furthermore, administration of LCN2 exacerbates the disease with significantly higher renal activity scores accompanied by increased Th1 cells. Importantly, circulating Th1 cells and IFN-γ levels are markedly increased in LN patients, and these changes are associated with increased LCN2 levels.

Conclusion: Collectively, our findings demonstrate LCN2 is a regulator of Th1 which could be a therapeutic target for the treatment of LN.


Disclosure: W. Chen, None; L. Sun, None.

To cite this abstract in AMA style:

Chen W, Sun L. Lipocalin-2 Exacerbates Lupus Nephritis by Promoting Th1 Cell Differentiation [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/lipocalin-2-exacerbates-lupus-nephritis-by-promoting-th1-cell-differentiation/. Accessed February 3, 2023.
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