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

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

doi:10.1038/ki.2015.280

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

Standard

The lymphotoxin β receptor is a potential therapeutic target in renal inflammation. / Seleznik, Gitta; Seeger, Harald; Bauer, Judith; Fu, Kai; Czerkowicz, Julie; Papandile, Adrian; Poreci, Uriana; Rabah, Dania; Ranger, Ann; Cohen, Clemens D; Lindenmeyer, Maja; Chen, Jin; Edenhofer, Ilka; Anders, Hans J; Lech, Maciej; Wüthrich, Rudolf P; Ruddle, Nancy H; Moeller, Marcus J; Kozakowski, Nicolas; Regele, Heinz; Browning, Jeffrey L; Heikenwalder, Mathias; Segerer, Stephan.

In: KIDNEY INT, Vol. 89, No. 1, 01.2016, p. 113-26.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Seleznik, G, Seeger, H, Bauer, J, Fu, K, Czerkowicz, J, Papandile, A, Poreci, U, Rabah, D, Ranger, A, Cohen, CD, Lindenmeyer, M, Chen, J, Edenhofer, I, Anders, HJ, Lech, M, Wüthrich, RP, Ruddle, NH, Moeller, MJ, Kozakowski, N, Regele, H, Browning, JL, Heikenwalder, M & Segerer, S 2016, 'The lymphotoxin β receptor is a potential therapeutic target in renal inflammation', KIDNEY INT, vol. 89, no. 1, pp. 113-26. https://doi.org/10.1038/ki.2015.280

APA

Seleznik, G., Seeger, H., Bauer, J., Fu, K., Czerkowicz, J., Papandile, A., Poreci, U., Rabah, D., Ranger, A., Cohen, C. D., Lindenmeyer, M., Chen, J., Edenhofer, I., Anders, H. J., Lech, M., Wüthrich, R. P., Ruddle, N. H., Moeller, M. J., Kozakowski, N., ... Segerer, S. (2016). The lymphotoxin β receptor is a potential therapeutic target in renal inflammation. KIDNEY INT, 89(1), 113-26. https://doi.org/10.1038/ki.2015.280

Vancouver

Seleznik G, Seeger H, Bauer J, Fu K, Czerkowicz J, Papandile A et al. The lymphotoxin β receptor is a potential therapeutic target in renal inflammation. KIDNEY INT. 2016 Jan;89(1):113-26. https://doi.org/10.1038/ki.2015.280

Bibtex

@article{9be7b1213e01481abfe114ccbda2f79e,

title = "The lymphotoxin β receptor is a potential therapeutic target in renal inflammation",

abstract = "Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.",

keywords = "Adult, Animals, Cell Line, Chemokines, Disease Models, Animal, Epithelial Cells, Female, Glomerulonephritis, IGA, Humans, Immunoglobulins, Kidney Glomerulus, Kidney Tubules, Ligands, Lupus Nephritis, Lymphocytes, Lymphotoxin beta Receptor, Lymphotoxin-alpha, Lymphotoxin-beta, Male, Mesangial Cells, Mice, Middle Aged, RNA, Messenger, Signal Transduction, Transcriptome, Journal Article, Research Support, Non-U.S. Gov't",

author = "Gitta Seleznik and Harald Seeger and Judith Bauer and Kai Fu and Julie Czerkowicz and Adrian Papandile and Uriana Poreci and Dania Rabah and Ann Ranger and Cohen, {Clemens D} and Maja Lindenmeyer and Jin Chen and Ilka Edenhofer and Anders, {Hans J} and Maciej Lech and W{\"u}thrich, {Rudolf P} and Ruddle, {Nancy H} and Moeller, {Marcus J} and Nicolas Kozakowski and Heinz Regele and Browning, {Jeffrey L} and Mathias Heikenwalder and Stephan Segerer",

year = "2016",

month = jan,

doi = "10.1038/ki.2015.280",

language = "English",

volume = "89",

pages = "113--26",

journal = "KIDNEY INT",

issn = "0085-2538",

publisher = "NATURE PUBLISHING GROUP",

number = "1",

}

RIS

TY - JOUR

T1 - The lymphotoxin β receptor is a potential therapeutic target in renal inflammation

AU - Seleznik, Gitta

AU - Seeger, Harald

AU - Bauer, Judith

AU - Fu, Kai

AU - Czerkowicz, Julie

AU - Papandile, Adrian

AU - Poreci, Uriana

AU - Rabah, Dania

AU - Ranger, Ann

AU - Cohen, Clemens D

AU - Lindenmeyer, Maja

AU - Chen, Jin

AU - Edenhofer, Ilka

AU - Anders, Hans J

AU - Lech, Maciej

AU - Wüthrich, Rudolf P

AU - Ruddle, Nancy H

AU - Moeller, Marcus J

AU - Kozakowski, Nicolas

AU - Regele, Heinz

AU - Browning, Jeffrey L

AU - Heikenwalder, Mathias

AU - Segerer, Stephan

PY - 2016/1

Y1 - 2016/1

N2 - Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.

AB - Accumulation of inflammatory cells in different renal compartments is a hallmark of progressive kidney diseases including glomerulonephritis (GN). Lymphotoxin β receptor (LTβR) signaling is crucial for the formation of lymphoid tissue, and inhibition of LTβR signaling has ameliorated several non-renal inflammatory models. Therefore, we tested whether LTβR signaling could also have a role in renal injury. Renal biopsies from patients with GN were found to express both LTα and LTβ ligands, as well as LTβR. The LTβR protein and mRNA were localized to tubular epithelial cells, parietal epithelial cells, crescents, and cells of the glomerular tuft, whereas LTβ was found on lymphocytes and tubular epithelial cells. Human tubular epithelial cells, mesangial cells, and mouse parietal epithelial cells expressed both LTα and LTβ mRNA upon stimulation with TNF in vitro. Several chemokine mRNAs and proteins were expressed in response to LTβR signaling. Importantly, in a murine lupus model, LTβR blockade improved renal function without the reduction of serum autoantibody titers or glomerular immune complex deposition. Thus, a preclinical mouse model and human studies strongly suggest that LTβR signaling is involved in renal injury and may be a suitable therapeutic target in renal diseases.

KW - Adult

KW - Animals

KW - Cell Line

KW - Chemokines

KW - Disease Models, Animal

KW - Epithelial Cells

KW - Female

KW - Glomerulonephritis, IGA

KW - Humans

KW - Immunoglobulins

KW - Kidney Glomerulus

KW - Kidney Tubules

KW - Ligands

KW - Lupus Nephritis

KW - Lymphocytes

KW - Lymphotoxin beta Receptor

KW - Lymphotoxin-alpha

KW - Lymphotoxin-beta

KW - Male

KW - Mesangial Cells

KW - Mice

KW - Middle Aged

KW - RNA, Messenger

KW - Signal Transduction

KW - Transcriptome

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1038/ki.2015.280

DO - 10.1038/ki.2015.280

M3 - SCORING: Journal article

C2 - 26398497

VL - 89

SP - 113

EP - 126

JO - KIDNEY INT

JF - KIDNEY INT

SN - 0085-2538

IS - 1

ER -