IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis

Michiya Shinozaki, Junichi Hirahashi, Tatiana Lebedeva, Foo Y. Liew, David J. Salant, Ruth Maron, Vicki Rubin Kelley

Research output: Contribution to journalArticle

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Abstract

IL-15, a T cell growth factor, has been linked to exacerbating autoimmune diseases and allograft rejection. To test the hypothesis that IL-15-deficient (IL-15-/-) mice would be protected from T cell-dependent nephritis, we induced nephrotoxic serum nephritis (NSN) in IL-15-/- and wild-type (IL-15+/+) C57BL/6 mice. Contrary to our expectations, IL-15 protects the kidney during this T cell-dependent immunologic insult. Tubular, interstitial, and glomerular pathology and renal function are worse in IL-15-/- mice during NSN. We detected a substantial increase in tubular apoptosis in IL-15-/- kidneys. Moreover, macrophages and CD4 T cells are more abundant in the interstitia and glomeruli in IL-15-/- mice. This led us to identify several mechanisms responsible for heightened renal injury in the absence of IL-15. We now report that IL-15 and the IL-15 receptor (α,β,γ chains) are constitutively expressed in normal tubular epithelial cells (TECs). IL-15 is an autocrine survival factor for TECs. TEC apoptosis induced with anti-Fas or actinomycin D is substantially greater in IL-15-/- than in wild-type TECs. Moreover, IL-15 decreases the induction of a nephritogenic chemokine, MCP-1, that attracts leukocytes into the kidney during NSN. Taken together, we suggest that IL-15 is a therapeutic for tubulointerstitial and glomerular kidney diseases.

Original languageEnglish
Pages (from-to)951-960
Number of pages10
JournalJournal of Clinical Investigation
Volume109
Issue number7
DOIs
Publication statusPublished - 2002
Externally publishedYes

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Interleukin-15
Nephritis
Epithelial Cells
Apoptosis
Inflammation
Kidney
T-Lymphocytes
Interleukin-15 Receptors
Serum
Kidney Diseases
Dactinomycin
Inbred C57BL Mouse
Chemokines
Autoimmune Diseases
Interleukin-2

ASJC Scopus subject areas

  • Medicine(all)

Cite this

IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis. / Shinozaki, Michiya; Hirahashi, Junichi; Lebedeva, Tatiana; Liew, Foo Y.; Salant, David J.; Maron, Ruth; Kelley, Vicki Rubin.

In: Journal of Clinical Investigation, Vol. 109, No. 7, 2002, p. 951-960.

Research output: Contribution to journalArticle

Shinozaki, Michiya ; Hirahashi, Junichi ; Lebedeva, Tatiana ; Liew, Foo Y. ; Salant, David J. ; Maron, Ruth ; Kelley, Vicki Rubin. / IL-15, a survival factor for kidney epithelial cells, counteracts apoptosis and inflammation during nephritis. In: Journal of Clinical Investigation. 2002 ; Vol. 109, No. 7. pp. 951-960.
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