The NZB/W F1 mouse model for Sjögren's syndrome: A historical perspective and lessons learned

Bagavant, Harini; Michrowska, Aleksandra; Deshmukh, Umesh S.

doi:10.1016/j.autrev.2020.102686

Cited by 12 publications

(2 citation statements)

References 87 publications

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“…Autoimmune induction of anti-TRIM21 antibodies has been explored in mouse models ( 178 ). In particular, the New Zealand Mixed 2758 (NZM2758) mouse strain, obtained by backcrossing and selectively breeding New Zealand Black and New Zealand White mice, has been used to model SS development ( 179 , 180 ).…”

Section: Anti-trim21 Antibody Development In Patients and Animal Modelsmentioning

confidence: 99%

TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

2021

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TRIM21 (Ro52/SSA1) is an E3 ubiquitin ligase with key roles in immune host defence, signal transduction, and possibly cell cycle regulation. It is also an autoantibody target in Sjögren’s syndrome, systemic lupus erythematosus, and other rheumatic autoimmune diseases. Here, we summarise the structure and function of this enzyme, its roles in innate immunity, adaptive immunity and cellular homeostasis, the pathogenesis of autoimmunity against TRIM21, and the potential impacts of autoantibodies to this intracellular protein.

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Section: Anti-trim21 Antibody Development In Patients and Animal Modelsmentioning

confidence: 99%

TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

2021

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“…B cell activating factor (BAFF) favors B cell proliferation, maturation and survival and is primarily induced by type I and type II interferons [25,26]. Animal models for SS have been pivotal in clarifying the role of pro-inflammatory cytokines in disease pathogenesis [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiologic role of Interleukin-33/ST2 in Sjögren's syndrome

Soyfoo

Nicaise

2021

Autoimmunity Reviews

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Therapeutic JAK1 Inhibition Reverses Lupus Nephritis in a Mouse Model and Demonstrates Transcriptional Changes Consistent With Human Disease

Twomey,

Perper,

Westmoreland

et al. 2024

ACR Open Rheumatology

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ObjectiveJanus kinase family members are essential for signaling by multiple cytokines, including many implicated in systemic lupus erythematosus (SLE) pathogenesis. To test whether inhibition of JAK1 signaling can be efficacious in SLE, we used a JAK1‐selective inhibitor (ABT‐317) and evaluated its ability to ameliorate disease in murine SLE.MethodsEfficacy of ABT‐317 was evaluated using NZB/W‐F1 mice treated prophylactically and therapeutically. Primary endpoints were proteinuria, survival, and saliva production. Other endpoints included histological analysis of kidneys and salivary glands, flow cytometric analysis of splenic cell populations, and gene expression analysis by RNA sequencing in the kidneys, salivary glands, and blood. Publicly available human kidney gene transcription data were used to assess the translatability of the mouse findings.ResultsABT‐317 was efficacious when dosed prophylactically and prevented disease for up to two months after treatment cessation. When dosed therapeutically, ABT‐317 quickly reversed severe proteinuria and restored saliva production, as well as diminished kidney and salivary gland inflammation. ABT‐317‐induced changes in glomerular morphology coincided with normalization of a human nephrotic gene signature, suggesting translatability to human lupus nephritis (LN).ConclusionJAK1 inhibition prevented and reversed kidney and salivary gland manifestations of murine lupus with long‐lasting effects after treatment cessation. These data, along with the presence of JAK1 and nephrotic gene signatures in human LN glomeruli, suggest that a JAK1‐selective inhibitor may be an effective therapeutic in the treatment of human SLE and LN.

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The NZB/W F1 mouse model for Sjögren's syndrome: A historical perspective and lessons learned

Cited by 12 publications

References 87 publications

TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

TRIM21/Ro52 - Roles in Innate Immunity and Autoimmune Disease

Pathophysiologic role of Interleukin-33/ST2 in Sjögren's syndrome

Therapeutic JAK1 Inhibition Reverses Lupus Nephritis in a Mouse Model and Demonstrates Transcriptional Changes Consistent With Human Disease

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