Dataset Information

Vasculature-Associated Lymphoid Tissue: A Unique Tertiary Lymphoid Tissue Correlates With Renal Lesions in Lupus Nephritis Mouse Model.

ABSTRACT: Lupus nephritis (LN) is a common complication in young patients and the most predominant cause of glomerulonephritis. Infiltrating immune cells and presence of immunocomplexes in the kidney are hallmarks of LN, which is closely associated with renal lesions (RLs). However, their regulatory mechanism in the kidney remains unclear, which is valuable for prevention of RL development. Here, we show the development of vasculature-associated lymphoid tissue (VALT) in LN, which is related to renal inflammatory cytokines, indicating that VALT is a unique tertiary lymphoid tissue. Transcriptomic analysis revealed different chemokines and costimulatory molecules for VALT induction and organization. Vascular and perivascular structures showed lymphoid tissue organization through lymphorganogenic chemokine production. Transcriptional profile and intracellular interaction also demonstrated antigen presentation, lymphocyte activity, clonal expansion, follicular, and germinal center activity in VALT. Importantly, VALT size was correlated with infiltrating immune cells in kidney and RLs, indicating its direct correlation with the development of RLs. In addition, dexamethasone administration reduced VALT size. Therefore, inhibition of VALT formation would be a novel therapeutic strategy against LN.

SUBMITTER: Masum MA

PROVIDER: S-EPMC7770167 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Vasculature-Associated Lymphoid Tissue: A Unique Tertiary Lymphoid Tissue Correlates With Renal Lesions in Lupus Nephritis Mouse Model.

Masum Md Abdul MA Ichii Osamu O Elewa Yaser Hosny Ali YHA Otani Yuki Y Namba Takashi T Kon Yasuhiro Y

Frontiers in immunology 20201215

Lupus nephritis (LN) is a common complication in young patients and the most predominant cause of glomerulonephritis. Infiltrating immune cells and presence of immunocomplexes in the kidney are hallmarks of LN, which is closely associated with renal lesions (RLs). However, their regulatory mechanism in the kidney remains unclear, which is valuable for prevention of RL development. Here, we show the development of vasculature-associated lymphoid tissue (VALT) in LN, which is related to renal infl ...[more]

PMID: 33384689

Similar Datasets

Project description:In lupus nephritis (LN), kidney inflammation may be followed by fibrosis and progressive decline in function. Transforming growth factor (TGF)-? is a notable mediator of fibrosis, but it has other beneficial roles, thus indicating a need for alternate therapeutic targets for inhibition of fibrosis. Connective tissue growth factor (CTGF) acts as a downstream mediator of TGF-? in promoting fibrosis, without mediating the immunosuppressive effects of TGF-?. Animal studies show that CTGF may have important roles in renal fibrosis, but data are limited in human subjects. The present study tested the hypothesis that renal CTGF mRNA expression is related to TGF-?1 and collagen I expression and is predictive of renal function deterioration in patients with LN (n=39). Gene expression was measured using multiplex real-time quantitative RT-PCR and renal function was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) glomerular filtration rate (GFR) equation. Decline in GFR was assessed by regression of GFR at biopsy to 1 year following biopsy. CTGF mRNA expression was significantly correlated with TGF-?1 and collagen I. GFR at biopsy was 89.2±39.2 ml/ min. Renal CTGF mRNA expression correlated inversely with baseline GFR. Renal CTGF mRNA was significantly higher in patients with moderate to severe CKD compared to those in the milder CKD group (low GFR 4.92±4.34 vs. high GFR 1.52±1.94, p<0.005). CTGF mRNA was also higher in patients with subsequent decline in GFR [GFR decline (5.19±4.46) vs. no GFR decline (1.79±1.97); P<0.01]. In conclusion, renal expression of CTGF was positively related to TGF-?1 and collagen I in patients with LN. Furthermore, high CTGF mRNA expression was associated with poor GFR at baseline and subsequent deterioration of kidney function. CTGF expression in the kidney may serve as an early marker for renal disease progression and could be evaluated as a target for therapeutic intervention to prevent renal failure in LN.

Dataset Information

Vasculature-Associated Lymphoid Tissue: A Unique Tertiary Lymphoid Tissue Correlates With Renal Lesions in Lupus Nephritis Mouse Model.

Publications

Vasculature-Associated Lymphoid Tissue: A Unique Tertiary Lymphoid Tissue Correlates With Renal Lesions in Lupus Nephritis Mouse Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets