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 language | English |
|---|---|
| Pages (from-to) | 494-503 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 161 |
| Issue number | 1 |
| Publication status | Published - 1 Jul 1998 |
| Externally published | Yes |
Cite this
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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 journal › Article › Research › peer-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 -