The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

Seleznik, Gitta Maria; Seeger, Harald; Bauer, Judith; Fu, Kai; Czerkowicz, Julie; Papandile, Adrian; Poreci, Uriana; Rabah, Dania; Ranger, Ann; Cohen, Clemens D.; Lindenmeyer, Maja T.; Chen, Jin; Edenhofer, Ilka; Anders, Hans Joachim; Lech, Maciej; Wüthrich, Rudolf P.; Ruddle, Nancy H.; Moeller, Marcus J.; Kozakowski, Nicolas; Regele, Heinz; Browning, Jeffrey L.; Heikenwälder, Mathias; Segerer, Stephan

doi:10.1038/ki.2015.280

Cited by 16 publications

(22 citation statements)

References 80 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To the best of our knowledge, this study is the first to demonstrate that both receptors play an instrumental role in kidney disease, whereas previous studies have focused on the effect of LTβR activation. 33 In addition, these data raised the fundamental question: by what mechanism does LIGHT aggravate LPS-induced SA-AKI? We speculated that there were two possible mechanisms.…”

Section: Discussionmentioning

confidence: 99%

LIGHT aggravates sepsis‐associated acute kidney injury via TLR4‐MyD88‐NF‐κB pathway

Zhong

Yang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection. 1,2 Sepsis most commonly results in multiorgan dysfunction, especially kidney dysfunction, namely sepsis-associated acute kidney injury (SA-AKI). It constitutes almost 50% of cases diagnosed with acute kidney injury in intensive care units (ICU). 3-7 Furthermore, SA-AKI increases the risk of chronic kidney disease and is a leading independent cause of high mortality. 2 Unlike any other phenotype of acute kidney injury (AKI), SA-AKI

show abstract

Section: Discussionmentioning

confidence: 99%

LIGHT aggravates sepsis‐associated acute kidney injury via TLR4‐MyD88‐NF‐κB pathway

Zhong

Yang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…An Fc fusion protein of LTβR, which can neutralize both LTαβ and LIGHT, can block disease symptoms in many mouse models of rheumatic disease, including collagen-induced and adjuvant arthritis, several models of SLE and the Sjögren-syndrome-like salivary gland inflammation of non-obese diabetic mice 131–133,145–148 . Additionally, genetic deletion of LIGHT protects mice from lung and skin inflammation and tissue remodelling in models of SSc 144,149 .…”

Section: Increasing Tissue Inflammationmentioning

confidence: 99%

Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases

2017

View full text Add to dashboard Cite

TNF blockers are highly efficacious at dampening inflammation and reducing symptoms in rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, and also in nonrheumatic syndromes such as inflammatory bowel disease. As TNF belongs to a superfamily of 19 structurally related proteins that have both proinflammatory and anti-inflammatory activity, reagents that disrupt the interaction between proinflammatory TNF family cytokines and their receptors, or agonize the anti-inflammatory receptors, are being considered for the treatment of rheumatic diseases. Biologic agents that block B cell activating factor (BAFF) and receptor activator of nuclear factor-κB ligand (RANKL) have been approved for the treatment of systemic lupus erythematosus and osteoporosis, respectively. In this Review, we focus on additional members of the TNF superfamily that could be relevant for the pathogenesis of rheumatic disease, including those that can strongly promote activity of immune cells or increase activity of tissue cells, as well as those that promote death pathways and might limit inflammation. We examine preclinical mouse and human data linking these molecules to the control of damage in the joints, muscle, bone or other tissues, and discuss their potential as targets for future therapy of rheumatic diseases.

show abstract

“…This is in line with the previously described constitutive expression of the receptor in parenchymal cells and its promotor region suggesting a house keeping function [ 45 ]. Also earlier studies from our group in patients with various forms of glomerulonephritis, demonstrated that LTβR expression was unaltered in inflamed kidneys [ 15 ].…”

Section: Discussionmentioning

confidence: 96%

“…We performed immunohistochemistry as previously described [ 15 , 32 ]. In brief, sections were dewaxed in xylene, rehydrated in a graded series of ethanol, and incubated in 3% hydrogen peroxide.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Lymphotoxin expression in human and murine renal allografts

Seeger¹,

Lindenmeyer²,

Cohen³

et al. 2018

PLoS ONE

Self Cite

View full text Add to dashboard Cite

The kidney is the most frequently transplanted solid organ. Recruitment of inflammatory cells, ranging from diffuse to nodular accumulations with defined microarchitecture, is a hallmark of acute and chronic renal allograft injury. Lymphotoxins (LTs) mediate the communication of lymphocytes and stromal cells and play a pivotal role in chronic inflammation and formation of lymphoid tissue. The aim of this study was to assess the expression of members of the LT system in acute rejection (AR) and chronic renal allograft injury such as transplant glomerulopathy (TG) and interstitial fibrosis/tubular atrophy (IFTA). We investigated differentially regulated components in transcriptomes of human renal allograft biopsies. By microarray analysis, we found the upregulation of LTβ, LIGHT, HVEM and TNF receptors 1 and 2 in AR and IFTA in human renal allograft biopsies. In addition, there was clear evidence for the activation of the NFκB pathway, most likely a consequence of LTβ receptor stimulation. In human renal allograft biopsies with transplant glomerulopathy (TG) two distinct transcriptional patterns of LT activation were revealed. By quantitative RT-PCR robust upregulation of LTα, LTβ and LIGHT was shown in biopsies with borderline lesions and AR. Immunohistochemistry revealed expression of LTβ in tubular epithelial cells and inflammatory infiltrates in transplant biopsies with AR and IFTA. Finally, activation of LT signaling was reproduced in a murine model of renal transplantation with AR. In summary, our results indicate a potential role of the LT system in acute renal allograft rejection and chronic transplant injury. Activation of the LT system in allograft rejection in rodents indicates a species independent mechanism. The functional role of the LT system in acute renal allograft rejection and chronic injury remains to be determined.

show abstract

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

Cited by 16 publications

References 80 publications

LIGHT aggravates sepsis‐associated acute kidney injury via TLR4‐MyD88‐NF‐κB pathway

LIGHT aggravates sepsis‐associated acute kidney injury via TLR4‐MyD88‐NF‐κB pathway

Beyond TNF: TNF superfamily cytokines as targets for the treatment of rheumatic diseases

Lymphotoxin expression in human and murine renal allografts

Contact Info

Product

Resources

About