Metabolic Regulation of Organelle Homeostasis in Lupus T Cells

Overview

Journal Clin Immunol

Specialty Allergy & Immunology

Date 2012 Jul 28

PMID 22836085

Citations 27

Authors

Tiffany N Caza

Gergely Talaber

Andras Perl

Affiliations

Soon will be listed here.

Abstract

Abnormal T-cell signaling and activation are characteristic features in systemic lupus erythematosus (SLE). Lupus T cells are shifted toward an over-activated state, important signaling pathways are rewired, and signaling molecules are replaced. Disturbances in metabolic and organelle homeostasis, importantly within the mitochondrial, endosomal, and autophagosomal compartments, underlie the changes in signal transduction. Mitochondrial hyperpolarization, enhanced endosomal recycling, and dysregulated autophagy are hallmarks of pathologic organelle homeostasis in SLE. This review is focused on the metabolic checkpoints of endosomal traffic that control immunological synapse formation and mitophagy and may thus serve as targets for treatment in SLE.

Citing Articles

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References

Fernandez D, Bonilla E, Mirza N, Niland B, Perl A . Rapamycin reduces disease activity and normalizes T cell activation-induced calcium fluxing in patients with systemic lupus erythematosus. Arthritis Rheum. 2006; 54(9):2983-8. PMC: 4034146. DOI: 10.1002/art.22085. View

Teachey D, Greiner R, Seif A, Attiyeh E, Bleesing J, Choi J . Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome. Br J Haematol. 2009; 145(1):101-6. PMC: 2819393. DOI: 10.1111/j.1365-2141.2009.07595.x. View

Dolff S, Abdulahad W, van Dijk M, Limburg P, Kallenberg C, Bijl M . Urinary T cells in active lupus nephritis show an effector memory phenotype. Ann Rheum Dis. 2010; 69(11):2034-41. DOI: 10.1136/ard.2009.124636. View

Ichinose K, Juang Y, Crispin J, Kis-Toth K, Tsokos G . Suppression of autoimmunity and organ pathology in lupus-prone mice upon inhibition of calcium/calmodulin-dependent protein kinase type IV. Arthritis Rheum. 2010; 63(2):523-9. PMC: 3030625. DOI: 10.1002/art.30085. View

Powell J, Lerner C, Schwartz R . Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation. J Immunol. 1999; 162(5):2775-84. View

Barber D, Bartolome A, Hernandez C, Flores J, Redondo C, Fernandez-Arias C . PI3Kgamma inhibition blocks glomerulonephritis and extends lifespan in a mouse model of systemic lupus. Nat Med. 2005; 11(9):933-5. DOI: 10.1038/nm1291. View

Zeng L, Xu L, Gutmann D, Wong M . Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol. 2008; 63(4):444-53. PMC: 3937593. DOI: 10.1002/ana.21331. View

Gros F, Arnold J, Page N, Decossas M, Korganow A, Martin T . Macroautophagy is deregulated in murine and human lupus T lymphocytes. Autophagy. 2012; 8(7):1113-23. PMC: 3429547. DOI: 10.4161/auto.20275. View

Quintana A, Hoth M . Mitochondrial dynamics and their impact on T cell function. Cell Calcium. 2012; 52(1):57-63. DOI: 10.1016/j.ceca.2012.02.005. View

10.

Wolf P, Ploegh H . How MHC class II molecules acquire peptide cargo: biosynthesis and trafficking through the endocytic pathway. Annu Rev Cell Dev Biol. 1995; 11:267-306. DOI: 10.1146/annurev.cb.11.110195.001411. View

11.

Hubbard V, Valdor R, Patel B, Singh R, Cuervo A, Macian F . Macroautophagy regulates energy metabolism during effector T cell activation. J Immunol. 2010; 185(12):7349-57. PMC: 3046774. DOI: 10.4049/jimmunol.1000576. View

12.

Daridon C, Blassfeld D, Reiter K, Mei H, Giesecke C, Goldenberg D . Epratuzumab targeting of CD22 affects adhesion molecule expression and migration of B-cells in systemic lupus erythematosus. Arthritis Res Ther. 2010; 12(6):R204. PMC: 3046510. DOI: 10.1186/ar3179. View

13.

Stirzaker R, Biswas P, Gupta S, Song L, Bhagat G, Pernis A . Administration of fasudil, a ROCK inhibitor, attenuates disease in lupus-prone NZB/W F1 female mice. Lupus. 2012; 21(6):656-61. DOI: 10.1177/0961203312436862. View

14.

Vyshkina T, Sylvester A, Sadiq S, Bonilla E, Canter J, Perl A . Association of common mitochondrial DNA variants with multiple sclerosis and systemic lupus erythematosus. Clin Immunol. 2008; 129(1):31-5. PMC: 2567049. DOI: 10.1016/j.clim.2008.07.011. View

15.

Wainszelbaum M, Proctor B, Pontow S, Stahl P, Alejandro Barbieri M . IL4/PGE2 induction of an enlarged early endosomal compartment in mouse macrophages is Rab5-dependent. Exp Cell Res. 2006; 312(12):2238-51. DOI: 10.1016/j.yexcr.2006.03.025. View

16.

Cardiel M, Tumlin J, Furie R, Wallace D, Joh T, Linnik M . Abetimus sodium for renal flare in systemic lupus erythematosus: results of a randomized, controlled phase III trial. Arthritis Rheum. 2008; 58(8):2470-80. DOI: 10.1002/art.23673. View

17.

Takahashi S, Kataoka H, Hara S, Yokosuka T, Takase K, Yamasaki S . In vivo overexpression of CTLA-4 suppresses lymphoproliferative diseases and thymic negative selection. Eur J Immunol. 2005; 35(2):399-407. DOI: 10.1002/eji.200324746. View

18.

Crispin J, Liossis S, Kis-Toth K, Lieberman L, Kyttaris V, Juang Y . Pathogenesis of human systemic lupus erythematosus: recent advances. Trends Mol Med. 2010; 16(2):47-57. PMC: 2823952. DOI: 10.1016/j.molmed.2009.12.005. View

19.

Florey O, Overholtzer M . Autophagy proteins in macroendocytic engulfment. Trends Cell Biol. 2012; 22(7):374-80. PMC: 3383932. DOI: 10.1016/j.tcb.2012.04.005. View

20.

Nagy G, Koncz A, Perl A . T cell activation-induced mitochondrial hyperpolarization is mediated by Ca2+- and redox-dependent production of nitric oxide. J Immunol. 2003; 171(10):5188-97. PMC: 4078644. DOI: 10.4049/jimmunol.171.10.5188. View