Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Faslpr mice

Deborah M. Lenda, E. Richard Stanley, Vicki R. Kelley

Research output: Contribution to journalArticle

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Abstract

Inflammation in the kidney and other tissues (lung, and salivary and lacrimal glands) is characteristic of MRL-Faslpr mice with features of lupus. Macrophages (Mφ) are prominent in these tissues. Given that 1) Mφ survival, recruitment, proliferation, and activation during inflammation is dependent on CSF-1, 2) Mφ mediate renal resident cell apoptosis, and 3) CSF-1 is up-regulated in MRL-Faslpr mice before, and during nephritis, we hypothesized that CSF-1-deficient MRL-Faslpr mice would be protected from Mφ-mediated nephritis, and the systemic illness. To test this hypothesis, we compared CSF-1-deficient MRL-Faslpr with wild-type strains. Renal pathology is suppressed and function improved in CSF-1-deficient MRL-Faslpr mice. There are far fewer intrarenal Mφ and T cells in CSF-1-deficient MRL-Faslpr vs wild-type kidneys. This leukocytic reduction results from suppressed infiltration, and intrarenal proliferation, but not enhanced apoptosis. The CSF-1-deficient MRL-Faslpr kidneys remain preserved as indicated by greatly reduced indices of injury (nephritogenic cytokines, tubular apoptosis, and proliferation). The renal protective mechanism in CSF-1-deficient mice is not limited to reduced intrarenal leukocytes; circulating Igs and autoantibodies, and renal Ig deposits are decreased. This may result from enhanced B cell apoptosis and fewer B cells in CSF-1-deficient MRL-Faslpr mice. Furthermore, the systemic illness including, skin, lung, and lacrimal and salivary glands pathology, lymphadenopathy, and splenomegaly are dramatically suppressed in CSF-1-deficient MRL-Faslpr as compared with wild-type mice. These results indicate that CSF-1 is an attractive therapeutic target to combat Mφ-, T cell-, and B cell-mediated autoimmune lupus.

Original languageEnglish (US)
Pages (from-to)4744-4754
Number of pages11
JournalJournal of Immunology
Volume173
Issue number7
StatePublished - Oct 1 2004

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Macrophage Colony-Stimulating Factor
Autoimmune Diseases
B-Lymphocytes
Macrophages
T-Lymphocytes
Kidney
Apoptosis
Lacrimal Apparatus
Nephritis
Salivary Glands
Pathology
Inflammation
Lung
Splenomegaly
Granulocyte-Macrophage Colony-Stimulating Factor
Autoantibodies
Leukocytes
Cytokines

ASJC Scopus subject areas

  • Immunology

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Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Faslpr mice. / Lenda, Deborah M.; Stanley, E. Richard; Kelley, Vicki R.

In: Journal of Immunology, Vol. 173, No. 7, 01.10.2004, p. 4744-4754.

Research output: Contribution to journalArticle

Lenda, Deborah M. ; Stanley, E. Richard ; Kelley, Vicki R. / Negative role of colony-stimulating factor-1 in macrophage, T cell, and B cell mediated autoimmune disease in MRL-Faslpr mice. In: Journal of Immunology. 2004 ; Vol. 173, No. 7. pp. 4744-4754.
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