Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice

Takashi Miwa, Lin Zhou, Michael A. Maldonado, Michael P. Madaio, Robert A. Eisenberg, Wen Chao Song

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

CD59 is a GPI-anchored membrane regulator of complement expressed on blood cells as well as peripheral tissues. It protects host cells from complement injury by inhibiting formation of the membrane attack complex. Recent studies in mice have suggested also a role of CD59 in T cell immune response that was mechanistically independent of complement. In the present study, we investigated the function of CD59 in the MRL/lpr model of murine lupus. We backcrossed the Cd59a knockout (Cd59a-/-) mouse onto the MRL/lpr background and compared Cd59a+/+-MRL/lpr and Cd59a-/--MRL/lpr littermates for the development of systemic autoimmunity. We found that CD59a deficiency significantly exacerbated the skin disease and lymphoproliferation characteristic of MRL/lpr mice. It also increased autoantibody titers and caused a higher level of proteinuria in male MRL/ lpr mice. Bone marrow transfer experiments indicated that CD59a expression on both bone marrow-derived cells and peripheral tissues played a role in lymphoproliferation, whereas the skin disease phenotype is determined mainly by local CD59a expression. Importantly, C3 gene deletion or C5 neutralization with a blocking mAb in Cd59a -/--MRL/lpr mice did not rescue the proautoimmune phenotype associated with CD59a deficiency. These results together suggest that CD59a inhibits systemic autoimmunity in MRL/lpr mice through a complement-independent mechanism.

Original languageEnglish (US)
Pages (from-to)5434-5441
Number of pages8
JournalJournal of Immunology
Volume189
Issue number11
DOIs
StatePublished - Dec 1 2012

Fingerprint

Inbred MRL lpr Mouse
Autoimmunity
Skin Diseases
Complement Membrane Attack Complex
Phenotype
Gene Deletion
Proteinuria
Knockout Mice
Bone Marrow Cells
Autoantibodies
Blood Cells
Bone Marrow
T-Lymphocytes
Membranes
Wounds and Injuries

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Miwa, T., Zhou, L., Maldonado, M. A., Madaio, M. P., Eisenberg, R. A., & Song, W. C. (2012). Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice. Journal of Immunology, 189(11), 5434-5441. https://doi.org/10.4049/jimmunol.1201621

Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice. / Miwa, Takashi; Zhou, Lin; Maldonado, Michael A.; Madaio, Michael P.; Eisenberg, Robert A.; Song, Wen Chao.

In: Journal of Immunology, Vol. 189, No. 11, 01.12.2012, p. 5434-5441.

Research output: Contribution to journalArticle

Miwa, T, Zhou, L, Maldonado, MA, Madaio, MP, Eisenberg, RA & Song, WC 2012, 'Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice', Journal of Immunology, vol. 189, no. 11, pp. 5434-5441. https://doi.org/10.4049/jimmunol.1201621
Miwa T, Zhou L, Maldonado MA, Madaio MP, Eisenberg RA, Song WC. Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice. Journal of Immunology. 2012 Dec 1;189(11):5434-5441. https://doi.org/10.4049/jimmunol.1201621
Miwa, Takashi ; Zhou, Lin ; Maldonado, Michael A. ; Madaio, Michael P. ; Eisenberg, Robert A. ; Song, Wen Chao. / Absence of CD59 exacerbates systemic autoimmunity in MRL/lpr mice. In: Journal of Immunology. 2012 ; Vol. 189, No. 11. pp. 5434-5441.
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