Lipocalin-2 is a pathogenic determinant and biomarker of neuropsychiatric lupus

Journal of Autoimmunity
Elise V MikeChaim Putterman

Abstract

Neuropsychiatric manifestations in lupus (NPSLE) affect ∼20-40% of patients. In the central nervous system, lipocalin-2 (LCN2) can promote injury through mechanisms directly linked to NPSLE, including brain barrier disruption, neurotoxicity, and glial activation. Since LCN2 is elevated in lupus and has been implicated in neuroinflammation, we investigated whether LCN2 is required for the pathogenesis of NPSLE. Here, we investigated the effects of LCN2 deficiency on the development of neurobehavioral deficits in the B6.Sle1.Sle3 (Sle1,3) mouse lupus model. Sle1,3 mice exhibited depression-like behavior and impaired spatial and recognition memory, and these deficits were attenuated in Sle1,3-LCN2KO mice. Whole-brain flow cytometry showed a significant increase in brain infiltrating leukocytes in Sle1,3 mice that was not reduced by LCN2 deficiency. RNA sequencing on sorted microglia revealed that several genes differentially expressed between B6 and Sle1,3 mice were regulated by LCN2, and that these genes are key mediators of the neuroinflammatory cascade. Importantly, LCN2 is upregulated in the cerebrospinal fluid of NPSLE patients across 2 different ethnicities. Our findings establish the Sle1,3 strain as an NPSLE model, demonst...Continue Reading

Citations

May 19, 2019·Arthritis & Rheumatology·Nina KelloBetty Diamond
Aug 16, 2019·Current Opinion in Rheumatology·Dionysis NikolopoulosDimitrios T Boumpas
Jan 3, 2020·Current Opinion in Rheumatology·Erica MooreChaim Putterman
Nov 15, 2020·Lupus Science & Medicine·Diane ApostolopoulosEric Morand
Mar 31, 2021·Current Rheumatology Reports·Aida ZarfeshaniBetty Diamond
Nov 7, 2020·Clinical Rheumatology·Thaís Evelyn KarnoppOdirlei André Monticielo
Jun 2, 2021·Journal of Neuroimmunology·Xiaoyue QiaoHuan Dou
Jul 4, 2021·Rheumatic Diseases Clinics of North America·Yudong Liu, Mariana J Kaplan
Jul 30, 2021·Ageing Research Reviews·Doortje W DekensPetrus J W Naudé
Sep 2, 2021·American Journal of Physiology. Lung Cellular and Molecular Physiology·Stephanie GuardadoTara M Nordgren
Dec 7, 2021·Frontiers in Immunology·Michelle W HuangChaim Putterman
Jan 12, 2022·Current Opinion in Rheumatology·Julius LindblomIoannis Parodis

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