Abstract
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease generated by deregulation of T cell–mediated B-cell activation, which results in glomerulonephritis and renal failure. Disease is treated with immunosuppressants and cytostatic agents that have numerous side effects. Here we examine the use of inhibitors of phosphoinositide 3-kinase (PI3K) γ, a lipid kinase that regulates inflammation, in the MRL-lpr mouse model of SLE. Treatment reduced glomerulonephritis and prolonged lifespan, suggesting that P13Kγ may be a useful target in the treatment of chronic inflammation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Inghirami, G., Simon, J., Balow, J.E. & Tsokos, G.C. Clin. Exp. Rheumatol. 6, 269–276 (1988).
Cervera, R., Jiménez, S., Font, J. & Ingelmo, M. J. Rheumatol. 6, 150–157 (2003).
Chatham, W.W. & Kimberly, R.P. Lupus 10, 140–147 (2001).
Singer, G.G., Carrera, A.C., Marshak-Rothstein, A., Martinez-A.C. & Abbas, A.K. Curr. Opin. Immunol. 6, 913–920 (1994).
Wakeland, E.K., Wandstrat, A.E., Liu, K. & Morel, L. Curr. Opin. Immunol. 11, 701–707 (1999).
Dai, C., Liu, Z., Zhou, H. & Li, L. Chin. Med. J. 114, 864–868 (2001).
Jevnikar, A.M., Grusby, M.J. & Glimcher, L.H. J. Exp. Med. 179, 1137–1143 (1994).
Lang, T.J., Nguyen, P. & Papadimitriou, J.C. J. Immunol. 171, 5795–5801 (2003).
Rodríguez-Borlado, L. et al. FASEB J. 14, 895–903 (2000).
Neidhart, M., Pataki, F., Michel, B.A. & Fehr, K. Schweiz. Med. Wochenschr. 126, 1922–1925 (1996).
Vanhaesebroeck, B., Ali, K., Bilancio, A., Geering, B. & Foukas, L.C. Trends Biochem. Sci. 30, 194–204 (2005).
Niculescu, F. et al. Arthritis Rheum. 48, 1071–1079 (2003).
Sasaki, T. et al. Science 287, 1040–1046 (2000).
Hirsch, E. et al. Science 287, 1049–1053 (2000).
Camps, M. et al. Nat. Med. 11, 936–943 (2005).
Acknowledgements
We thank M.C. Moreno-Ortíz for cytofluorometry studies, P. Pallares, J. Martín and L. Gómez for animal work, A. Quadropani and the Serono team for technical advice and C. Mark for editorial assistance. D.F.B. has a Ramón y Cajal contract from the Spanish Ministry of Education and Science. This work was supported by grants from the Ramon Areces Fundation, European Union (QLRT2001-02171), the Community of Madrid (8.3/0030/2000) and the Spanish Dirección General de Ciencia y Desarrollo Tecnológico (SAF2001.2278). The Department of Immunology and Oncology was founded and is supported by the Spanish Council for Scientific Research and by Pfizer.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing financial interests.
Supplementary information
Supplementary Fig. 1
Different cell types in splenocytes from Control, Dexamethasone- and AS605240-treated MRL-lpr mice. (PDF 412 kb)
Supplementary Fig. 2
Proportion and absolute numbers of memory cells in splenocytes from Control, Dexamethasone- and AS605240-treated MRL-lpr mice. (PDF 352 kb)
Supplementary Table 1
SLE-like disease in AS605240-treated MRL-lpr mice. (PDF 51 kb)
Rights and permissions
About this article
Cite this article
Barber, D., Bartolomé, A., Hernandez, C. et al. PI3Kγ inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat Med 11, 933–935 (2005). https://doi.org/10.1038/nm1291
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nm1291
This article is cited by
-
SHP2: its association and roles in systemic lupus erythematosus
Inflammation Research (2023)
-
The role of PI3Kγ in the immune system: new insights and translational implications
Nature Reviews Immunology (2022)
-
Immunological pathogenesis and treatment of systemic lupus erythematosus
World Journal of Pediatrics (2020)
-
CircIBTK inhibits DNA demethylation and activation of AKT signaling pathway via miR-29b in peripheral blood mononuclear cells in systemic lupus erythematosus
Arthritis Research & Therapy (2018)
-
Canonical PI3Kγ signaling in myeloid cells restricts Trypanosoma cruzi infection and dampens chagasic myocarditis
Nature Communications (2018)