| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
-Dependent Autoimmune Kidney Disease in MRL-Faslpr Mice1
*
Laboratory of Molecular Autoimmune Disease, Renal Division, and
Center for Neurological Disease, Brigham and Women’s Hospital, Boston, MA 02115
IL-12 is secreted by kidney tubular epithelial cells in autoimmune
MRL-Faslpr mice before renal injury and
increases with advancing disease. Because IL-12 is a potent inducer of
IFN-
, the purpose of this study was to determine whether local
provision of IL-12 elicits IFN--secreting T cells within the kidney,
which, in turn, incites injury in
MRL-Faslpr mice. We used an ex vivo
retroviral gene transfer strategy to construct IL-12-secreting
MRL-Faslpr tubular epithelial cells
(IL-12 "carrier cells"), which were implanted under the kidney
capsule of MRL-Faslpr mice before renal
disease for a sustained period (28 days). IL-12 "carrier cells"
generated intrarenal and systemic IL-12. IL-12 fostered a marked,
well-demarcated accumulation of CD4, CD8, and double negative
(CD4-CD8- B220+) T cells
adjacent to the implant site. We detected more IFN--producing T
cells (CD4 > CD8 > CD4-CD8-
B220+) at 28 days (73 ± 14%) as compared with 7 days
(20 ± 8%) after implanting the IL-12 "carrier cells;" the
majority of these cells were proliferating (60–70%). By comparison,
an increase in systemic IL-12 resulted in a diffuse acceleration of
pathology in the contralateral (unimplanted) kidney. IFN- was
required for IL-12-incited renal injury, because IL-12 "carrier
cells" failed to elicit injury in
MRL-Faslpr kidneys genetically deficient
in IFN- receptors. Furthermore, IFN- "carrier cells" elicited
kidney injury in wild-type MRL-Faslpr
mice. Taken together, IL-12 elicits autoimmune injury by fostering the
accumulation of IFN--secreting CD4, CD8, and
CD4-CD8- B220+ T cells
within the kidney, which, in turn, promote a cascade of events
culminating in autoimmune kidney disease in
MRL-Faslpr mice.
This article has been cited by other articles:
|
|
 |
|
  P. D. Doodes, Y. Cao, K. M. Hamel, Y. Wang, B. Farkas, Y. Iwakura, and A. Finnegan Development of Proteoglycan-Induced Arthritis Is Independent of IL-17 J. Immunol., July 1, 2008; 181(1): 329 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, K. Hasegawa, Y. Sasaki, T. Mori, C. Adachi, and K. Maeda Systemic administration of interleukin-4 expressing plasmid DNA delays the development of glomerulonephritis and prolongs survival in lupus-prone female NZB x NZW F1 mice Nephrol. Dial. Transplant., November 1, 2007; 22(11): 3131 - 3138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Kokeny, M. Godo, E. Nagy, M. Kardos, K. Kotsch, P. Casalis, C. Bodor, L. Rosivall, H-D. Volk, A.C. Zenclussen, et al. Skin disease is prevented but nephritis is accelerated by multiple pregnancies in autoimmune MRL/LPR mice Lupus, July 1, 2007; 16(7): 465 - 477. [Abstract] [PDF]
|
|
|
|
 |
|
 P. Bobe, D. Bonardelle, K. Benihoud, P. Opolon, and M. K. Chelbi-Alix Arsenic trioxide: a promising novel therapeutic agent for lymphoproliferative and autoimmune syndromes in MRL/lpr mice Blood, December 15, 2006; 108(13): 3967 - 3975. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Neumann, T. Tschernig, D. Popa, A. Schmiedl, G. P. de Lema, K. Resch, and M. U. Martin Injection of IL-12- and IL-18-encoding plasmids ameliorates the autoimmune pathology of MRL/Mp-Tnfrsf6lpr mice: synergistic effect on autoimmune symptoms Int. Immunol., December 1, 2006; 18(12): 1779 - 1787. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Kitching More Targeted Treatments for Lupus Nephritis: Is the Future (Nearly) Here? J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3146 - 3148. [Full Text] [PDF]
|
|
|
|
|
|
A. Schwarting, K. Paul, S. Tschirner, J. Menke, T. Hansen, W. Brenner, V. R. Kelley, M. Relle, and P. R. Galle Interferon-{beta}: A Therapeutic for Autoimmune Lupus in MRL-Faslpr Mice J. Am. Soc. Nephrol., November 1, 2005; 16(11): 3264 - 3272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Patole, H.-J. Grone, S. Segerer, R. Ciubar, E. Belemezova, A. Henger, M. Kretzler, D. Schlondorff, and H.-J. Anders Viral Double-Stranded RNA Aggravates Lupus Nephritis through Toll-Like Receptor 3 on Glomerular Mesangial Cells and Antigen-Presenting Cells J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1326 - 1338. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kinoshita, T. Yamagata, Y. Nozaki, M. Sugiyama, S. Ikoma, M. Funauchi, and A. Kanamaru Blockade of IL-18 Receptor Signaling Delays the Onset of Autoimmune Disease in MRL-Faslpr Mice J. Immunol., October 15, 2004; 173(8): 5312 - 5318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. Lenda, E. R. Stanley, and V. R. Kelley Negative Role of Colony-Stimulating Factor-1 in Macrophage, T Cell, and B Cell Mediated Autoimmune Disease in MRL-Faslpr Mice J. Immunol., October 1, 2004; 173(7): 4744 - 4754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Kikawada, D. M. Lenda, and V. R. Kelley IL-12 Deficiency in MRL-Faslpr Mice Delays Nephritis and Intrarenal IFN-{gamma} Expression, and Diminishes Systemic Pathology J. Immunol., April 1, 2003; 170(7): 3915 - 3925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yin, G. Bahtiyar, N. Zhang, L. Liu, P. Zhu, M. E. Robert, J. McNiff, M. P. Madaio, and J. Craft IL-10 Regulates Murine Lupus J. Immunol., August 15, 2002; 169(4): 2148 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. E. Carvalho-Pinto, M. I. Garcia, M. Mellado, J. M. Rodriguez-Frade, J. Martin-Caballero, J. Flores, C. Martinez-A, and D. Balomenos Autocrine Production of IFN-{gamma} by Macrophages Controls Their Recruitment to Kidney and the Development of Glomerulonephritis in MRL/lpr Mice J. Immunol., July 15, 2002; 169(2): 1058 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kinoshita, G. Tesch, A. Schwarting, R. Maron, A. H. Sharpe, and V. R. Kelley Costimulation by B7-1 and B7-2 Is Required for Autoimmune Disease in MRL-Faslpr Mice J. Immunol., June 1, 2000; 164(11): 6046 - 6056. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
