Group 3 Innate Lymphoid Cells (ILC3s) Accelerate Lupus Nephritis Development by Promoting B Cell Activation in Kidney Ectopic Lymphoid Structures
- Glomerular Diseases: From Inflammation to Fibrosis - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
- Li, Feng, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Zhou, Yi, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
Group 3 innate lymphoid cells (ILC3s), a novel subset of immune cells with the features of both innate and adaptive immunity, have emerged as important players in autoimmune diseases. However, whether they participate in lupus nephritis (LN) remains elusive. Here, we investigated the role of ILC3s in the pathogenesis of LN.
Systemic and renal ILC3s were detected by flow cytometry or confocal microscopy in LN patients and spontaneous lupus model MRL/lpr mice. The distribution of ILC3s in human and murine kidneys were characterized by immunofluorescence, and the characteristics of ILC3s in different organs of MRL/lpr mice were revealed by transcriptome sequencing. Furthermore, ILC3s were adoptively transferred into LN mice to explore their roles in disease. In vitro, ILC3s were co-cultured with or without B cells to clarify their function in antibody formation.
The frequencies of ILC3s in blood and kidneys of LN patients were found significantly higher than normal control, and positively associated with serum anti-dsDNA, ANA and total IgG. The elevation of ILC3s and their correlations with autoantibodies were also observed in MRL/lpr mice. In the kidney, ILC3s were mainly localized within perivascular ectopic lymphoid structures, showing low expression of resident and proliferative markers. Interestingly, renal ILC3s shared high transcriptomic similarity with gut-derived ILC3s, implying that the small intestine may be a potential source of renal ILC3s. After adoptive transfer of ILC3s into LN mice, both systemic autoimmune manifestations and renal damage were significantly exacerbated. Meanwhile, there were remarkable increases in the proportion of plasma cells and IgG+ B cells in the kidney after ILC3s transfer. Mechanistically, in vitro studies showed that ILC3s promoted the differentiation of B cells into plasma cells and antibody formation.
Our results showed that ILC3s were increased in LN, and accelerated the progression of LN by promoting B cell activation in the kidney.
- Government Support – Non-U.S.