Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction

Han, Hui; Zhu, Jinzhou; Wang, Yaqiong; Zhu, Zhaowei; Chen, Yanjia; Lü, Lin; Jin, Wei; Yan, Xiaoxiang; Zhang, Ruiyan

doi:10.1002/path.4831

Cited by 38 publications

(40 citation statements)

References 30 publications

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“…Tapmeier et al [40] found a critical role for CD4(+) Kidney Dis 2020;6:150-156 DOI: 10.1159/000506201 T cells in kidney fibrosis using lymphopenic RAG(-/-) mice after ureteric obstruction. In addition, early-stage accumulation of B cells in the kidney accelerated monocyte/macrophage mobilization and infiltration and aggravated the renal fibrosis [41].…”

Section: Lvs Serve As a Bridge Between Innate And Adaptive Immunitymentioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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Background: Lymphatic vessels transport lymph away from microvascular beds into the cardiovascular system. The basic function of the lymphatic system include absorption of wa ter and macromolecules in the interstitial fluid, which plays an important role in maintaining osmotic balance of the body. Recent studies have shown that lymphangiogenesis is associated with tumor metabolism, injury repair, and chron ic inflammation, and deteriorates disease progression via immune cell trafficking. Summary: Renal interstitial lymph angiogenesis is found in patients with chronic kidney dis ease and a series of animal models of renal fibrosis. Lymphat ic vessels transfer antigen and antigenpresenting cells from peripheral tissues to lymph nodes, which initiates adaptive immunity and in turn deteriorates renal inflammation and renal fibrosis, even in nonautoimmune renal diseases. Key Messages: This review summarizes the latest findings on how lymphatics participate in the progression of chronic kid ney disease. This discussion will serve to highlight the role of adaptive immunity in noninfectious and nonautoimmune nephropathy, in order to provide new ideas and methods for prevention and treatment of kidney diseases.

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Section: Lvs Serve As a Bridge Between Innate And Adaptive Immunitymentioning

confidence: 99%

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Pei

Zeng

et al. 2020

Kidney Dis

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“…These chemokines are responsible for the recruitment of inflammatory cells, which, when activated, produce more cytokines to sustain and enhance inflammation. MCP-1 recruits macrophages into renal interstitium [27,28,29]. Our study showed that Ruxolitinib treatment reduced MCP-1 expression as well as macrophage infiltration in the obstructed kidneys.…”

Section: Discussionmentioning

confidence: 52%

Ruxolitinib Alleviates Renal Interstitial Fibrosis in UUO Mice

et al. 2020

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Ruxolitinib is a selective inhibitor of Jak1/2. Downstream signaling pathways of Jak, such as Stat3 and Akt/mTOR, are overactivated and contribute to renal interstitial fibrosis. Therefore, we explored the effect of Ruxolitinib on this pathological process. Unilateral ureteral obstruction (UUO) models and TGF-β1-treated fibroblasts and renal tubular epithelial cells were adopted in this study. Ruxolitinib was administered to UUO mice and TGF-β1-treated cells. Kidneys from UUO mice with Ruxolitinib treatment displayed less tubular injuries compared with those without Ruxolitinib treatment. Ruxolitinib treatment suppressed fibroblast activation and extracellular matrix (ECM) production in UUO kidneys and TGF-β1-treated fibroblasts. Ruxolitinib treatment also blocked epithelial-mesenchymal transition (EMT) in UUO kidneys and TGF-β 1-treated renal tubular epithelial cells. Moreover, Ruxolitinib treatment alleviated UUO-induced inflammation, oxidative stress and apoptosis. Mechanistically, Ruxolitinib treatment attenuated activation of both Stat3 and Akt/mTOR/Yap pathways. In conclusion, Ruxolitinib treatment can ameliorate UUO-induced renal interstitial fibrosis, suggesting that Ruxolitinib may be potentially used to treat fibrotic kidney disease.

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“…However, some studies suggested that B cell infiltration after AKI might hinder normal wound healing 31 . Interestingly, recent studies also suggested that infiltrated lymphocytes directly affected renal fibrosis by increasing levels of TGF-β 1 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

Diabetes Aggravates Post-ischaemic Renal Fibrosis through Persistent Activation of TGF-β1 and Shh Signalling

Kim

Kang

Park

et al. 2017

Sci Rep

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Diabetes is a risk factor for acute kidney injury (AKI) and chronic kidney disease (CKD). Diabetic patients are easy to progress to CKD after AKI. Currently, activation of fibrotic signalling including transforming growth factor-β1 (TGF-β1) is recognized as a key mechanism in CKD. Here, we investigated the influence of diabetes on CKD progression after AKI by using a unilateral renal ischaemia–reperfusion injury (IRI) model in diabetic mice. IRI induced extensive tubular injury, fibrosis and lymphocyte recruitment at 3 weeks after IRI, irrespective of diabetes. However, diabetes showed sustained tubular injury and markedly increased fibrosis and lymphocyte recruitment compared with non-diabetes at 5 week after IRI. The mRNAs and proteins related to TGF-β1 and sonic hedgehog (Shh) signalling were significantly higher in diabetic versus non-diabetic IRI kidneys. During the in vitro study, the hyperglycaemia induced the activation of TGF-β1 and Shh signalling and also increased profibrogenic phenotype change. However, hyperglycaemic control with insulin did not improve the progression of renal fibrosis and the activation of TGF-β1 and Shh signalling. In conclusion, diabetes promotes CKD progression of AKI via activation of the TGF-β1 and Shh signalling pathways, but insulin treatment was not enough for preventing the progression of renal fibrosis.

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Renal recruitment of B lymphocytes exacerbates tubulointerstitial fibrosis by promoting monocyte mobilization and infiltration after unilateral ureteral obstruction

Abstract: Renal fibrosis is a significant threat to public health globally. Diverse primary aetiologies eventually result in chronic kidney disease (

Cited by 38 publications

References 30 publications

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Lymphatic Vessels Enhancing Adaptive Immunity Deteriorates Renal Inflammation and Renal Fibrosis

Ruxolitinib Alleviates Renal Interstitial Fibrosis in UUO Mice

Diabetes Aggravates Post-ischaemic Renal Fibrosis through Persistent Activation of TGF-β1 and Shh Signalling

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