IFN-γ receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice

Andreas Schwarting, Takashi Wada, Koji Kinoshita, Gregory Tesch, Vicki Rubin Kelley

Research output: Contribution to journalArticleResearchpeer-review

Abstract

CSF-1 and TNF-α in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL- Fas(lpr) kidney, infiltrating T cells that secrete IFN-γ are a hallmark of disease. To examine the impact of IFN-γ on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-γR-deficient strain. In MRL-Fas(lpr) mice lacking IFN-γR, circulating and intrarenal CSF-1 were absent, TNF-α was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-γR induced CSF-1 and TNF-α in MRL. Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-γR induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-α induces apoptosis in MC, but not TEC, of the MRL-Fas(tpr) strain. Thus, IFN-γ is directly and indirectly responsible for apoptosis of TFC and MC in MRL-Fas(tpr) mice, respectively. In conclusion, IFN-γR signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-α), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.

Original languageEnglish
Pages (from-to)494-503
Number of pages10
JournalJournal of Immunology
Volume161
Issue number1
Publication statusPublished - 1 Jul 1998
Externally publishedYes

Cite this

Schwarting, Andreas ; Wada, Takashi ; Kinoshita, Koji ; Tesch, Gregory ; Kelley, Vicki Rubin. / IFN-γ receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice. In: Journal of Immunology. 1998 ; Vol. 161, No. 1. pp. 494-503.
@article{40b91bcf955a4027ad35f5f365166ec7,
title = "IFN-γ receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice",
abstract = "CSF-1 and TNF-α in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL- Fas(lpr) kidney, infiltrating T cells that secrete IFN-γ are a hallmark of disease. To examine the impact of IFN-γ on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-γR-deficient strain. In MRL-Fas(lpr) mice lacking IFN-γR, circulating and intrarenal CSF-1 were absent, TNF-α was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-γR induced CSF-1 and TNF-α in MRL. Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-γR induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-α induces apoptosis in MC, but not TEC, of the MRL-Fas(tpr) strain. Thus, IFN-γ is directly and indirectly responsible for apoptosis of TFC and MC in MRL-Fas(tpr) mice, respectively. In conclusion, IFN-γR signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-α), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.",
author = "Andreas Schwarting and Takashi Wada and Koji Kinoshita and Gregory Tesch and Kelley, {Vicki Rubin}",
year = "1998",
month = "7",
day = "1",
language = "English",
volume = "161",
pages = "494--503",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "1",

}

IFN-γ receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice. / Schwarting, Andreas; Wada, Takashi; Kinoshita, Koji; Tesch, Gregory; Kelley, Vicki Rubin.

In: Journal of Immunology, Vol. 161, No. 1, 01.07.1998, p. 494-503.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - IFN-γ receptor signaling is essential for the initiation, acceleration, and destruction of autoimmune kidney disease in MRL-Fas(lpr) mice

AU - Schwarting, Andreas

AU - Wada, Takashi

AU - Kinoshita, Koji

AU - Tesch, Gregory

AU - Kelley, Vicki Rubin

PY - 1998/7/1

Y1 - 1998/7/1

N2 - CSF-1 and TNF-α in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL- Fas(lpr) kidney, infiltrating T cells that secrete IFN-γ are a hallmark of disease. To examine the impact of IFN-γ on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-γR-deficient strain. In MRL-Fas(lpr) mice lacking IFN-γR, circulating and intrarenal CSF-1 were absent, TNF-α was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-γR induced CSF-1 and TNF-α in MRL. Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-γR induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-α induces apoptosis in MC, but not TEC, of the MRL-Fas(tpr) strain. Thus, IFN-γ is directly and indirectly responsible for apoptosis of TFC and MC in MRL-Fas(tpr) mice, respectively. In conclusion, IFN-γR signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-α), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.

AB - CSF-1 and TNF-α in the kidney of MRL-Fas(lpr) mice are proximal events that precede and promote autoimmune lupus nephritis, while apoptosis of renal parenchymal cells is a feature of advanced human lupus nephritis. In the MRL- Fas(lpr) kidney, infiltrating T cells that secrete IFN-γ are a hallmark of disease. To examine the impact of IFN-γ on renal injury in MRL-Fas(lpr) mice, we constructed a IFN-γR-deficient strain. In MRL-Fas(lpr) mice lacking IFN-γR, circulating and intrarenal CSF-1 were absent, TNF-α was markedly reduced, survival was extended, lymphadenopathy and splenomegaly were prevented, and the kidneys remained protected from destruction. Mesangial cells (MC) that were signaled through the IFN-γR induced CSF-1 and TNF-α in MRL. Fas(lpr) mice. We detected a large number of apoptotic renal parenchymal cells in advanced nephritis and determined that signaling via the IFN-γR induces apoptosis of tubular epithelial cells (TEC), but not MC. By comparison, TNF-α induces apoptosis in MC, but not TEC, of the MRL-Fas(tpr) strain. Thus, IFN-γ is directly and indirectly responsible for apoptosis of TFC and MC in MRL-Fas(tpr) mice, respectively. In conclusion, IFN-γR signaling is essential for the initiation (CSF-1), acceleration (CSF-1 and TNF-α), and apoptotic destruction of renal parenchymal cells in MRL-Fas(lpr) autoimmune kidney disease.

UR - http://www.scopus.com/inward/record.url?scp=0031831859&partnerID=8YFLogxK

M3 - Article

VL - 161

SP - 494

EP - 503

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 1

ER -