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Updated: Jul 12, 2025
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Analyses of Proteinuria, Renal Infiltration of Leukocytes, and Renal Deposition of Proteins in Lupus-prone MRL/lpr Mice
Published on: June 8, 2022
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Group 3 Innate Lymphoid Cells Exacerbate Lupus Nephritis by Promoting B Cell Activation in Kidney Ectopic Lymphoid
Feng Li1,2, Zhou Liang1,2, Haojie Zhong2,3
1Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 2, 2023
Summary
Group 3 innate lymphoid cells (ILC3s) increase in lupus nephritis (LN) and drive disease progression. Targeting these cells and their Delta-like1 (DLL1) interactions offers a potential therapeutic strategy for LN.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Group 3 innate lymphoid cells (ILC3s) are crucial immune regulators, but their specific role in lupus nephritis (LN) pathogenesis is not well understood.
- Existing research has not elucidated the origin and function of ILC3s within the context of LN.
Purpose of the Study:
- To investigate the role of ILC3s in the development and progression of lupus nephritis.
- To determine the origin and migratory patterns of ILC3s in LN.
- To explore the molecular mechanisms by which ILC3s contribute to LN pathology and evaluate potential therapeutic targets.
Main Methods:
- Analysis of ILC3 populations in human and murine LN samples.
- Utilizing MRL/lpr lupus mice and a nephrotoxic serum-induced LN model.
- Tracking ILC3 migration from the intestine to the kidney.
- Investigating the interaction between ILC3s, B cells, and ectopic lymphoid structures (ELS) in the kidney.
- Employing Delta-like1 (DLL1)/Notch pathway inhibition as a therapeutic intervention.
Main Results:
- Systemic and renal ILC3 accumulation correlates with LN disease severity.
- Kidney-infiltrating ILC3s predominantly originate from the intestine.
- Intestinal ILC3s exacerbate LN by promoting autoimmunity and kidney damage.
- ILC3s in LN kidneys activate B cells within ectopic lymphoid structures (ELS) via DLL1/Notch signaling, enhancing plasma cell differentiation and antibody production.
- Blocking DLL1 ameliorates ILC3-mediated pathology and protects against LN.
Conclusions:
- ILC3s play a significant pathogenic role in lupus nephritis by driving B cell activation and ectopic lymphoid structure formation.
- Intestinal ILC3s are a key contributor to LN progression.
- Targeting the DLL1/Notch pathway offers a promising therapeutic avenue for managing lupus nephritis.
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