Abnormalities of T Cell Signaling in Systemic Lupus Erythematosus

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2011 Apr 5

PMID 21457530

Citations 84

Authors

Vaishali R Moulton

George C Tsokos

Affiliations

Soon will be listed here.

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease resulting from a loss of tolerance to multiple self antigens, and characterized by autoantibody production and inflammatory cell infiltration in target organs, such as the kidneys and brain. T cells are critical players in SLE pathophysiology as they regulate B cell responses and also infiltrate target tissues, leading to tissue damage. Abnormal signaling events link to defective gene transcription and altered cytokine production, contributing to the aberrant phenotype of T cells in SLE. Study of signaling and gene transcription abnormalities in SLE T cells has led to the identification of novel targets for therapy.

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References

Nambiar M, Fisher C, Kumar A, Tsokos C, Warke V, Tsokos G . Forced expression of the Fc receptor gamma-chain renders human T cells hyperresponsive to TCR/CD3 stimulation. J Immunol. 2003; 170(6):2871-6. DOI: 10.4049/jimmunol.170.6.2871. View

Wong C, Lit L, Shan Tam L, Li E, Wong P, Kei Lam C . Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol. 2008; 127(3):385-93. DOI: 10.1016/j.clim.2008.01.019. View

Liu M, Liu H, Wang C, Lei H . Expression of CTLA-4 molecule in peripheral blood T lymphocytes from patients with systemic lupus erythematosus. J Clin Immunol. 1998; 18(6):392-8. DOI: 10.1023/a:1023226621966. View

Li Y, Zhao M, Yin H, Gao F, Wu X, Luo Y . Overexpression of the growth arrest and DNA damage-induced 45alpha gene contributes to autoimmunity by promoting DNA demethylation in lupus T cells. Arthritis Rheum. 2010; 62(5):1438-47. DOI: 10.1002/art.27363. View

Detre C, Keszei M, Romero X, Tsokos G, Terhorst C . SLAM family receptors and the SLAM-associated protein (SAP) modulate T cell functions. Semin Immunopathol. 2010; 32(2):157-71. PMC: 2868096. DOI: 10.1007/s00281-009-0193-0. View

Odegard J, DiPlacido L, Greenwald L, Kashgarian M, Kono D, Dong C . ICOS controls effector function but not trafficking receptor expression of kidney-infiltrating effector T cells in murine lupus. J Immunol. 2009; 182(7):4076-84. PMC: 2746004. DOI: 10.4049/jimmunol.0800758. View

Deng G, Liu L, Bahjat F, Pine P, Tsokos G . Suppression of skin and kidney disease by inhibition of spleen tyrosine kinase in lupus-prone mice. Arthritis Rheum. 2010; 62(7):2086-92. PMC: 2902591. DOI: 10.1002/art.27452. View

Richardson B . Primer: epigenetics of autoimmunity. Nat Clin Pract Rheumatol. 2007; 3(9):521-7. DOI: 10.1038/ncprheum0573. View

Nambiar M, Fisher C, Warke V, Krishnan S, Mitchell J, Delaney N . Reconstitution of deficient T cell receptor zeta chain restores T cell signaling and augments T cell receptor/CD3-induced interleukin-2 production in patients with systemic lupus erythematosus. Arthritis Rheum. 2003; 48(7):1948-55. DOI: 10.1002/art.11072. View

10.

Krishnan S, Kiang J, Fisher C, Nambiar M, Nguyen H, Kyttaris V . Increased caspase-3 expression and activity contribute to reduced CD3zeta expression in systemic lupus erythematosus T cells. J Immunol. 2005; 175(5):3417-23. DOI: 10.4049/jimmunol.175.5.3417. View

11.

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

12.

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

13.

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

14.

Gorelik G, Fang J, Wu A, Sawalha A, Richardson B . Impaired T cell protein kinase C delta activation decreases ERK pathway signaling in idiopathic and hydralazine-induced lupus. J Immunol. 2007; 179(8):5553-63. DOI: 10.4049/jimmunol.179.8.5553. View

15.

Sunahori K, Juang Y, Tsokos G . Methylation status of CpG islands flanking a cAMP response element motif on the protein phosphatase 2Ac alpha promoter determines CREB binding and activity. J Immunol. 2009; 182(3):1500-8. PMC: 2676107. DOI: 10.4049/jimmunol.182.3.1500. View

16.

Deng C, Kaplan M, Yang J, Ray D, Zhang Z, McCune W . Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients. Arthritis Rheum. 2001; 44(2):397-407. DOI: 10.1002/1529-0131(200102)44:2<397::AID-ANR59>3.0.CO;2-N. View

17.

Tenbrock K, Kyttaris V, Ahlmann M, Ehrchen J, Tolnay M, Melkonyan H . The cyclic AMP response element modulator regulates transcription of the TCR zeta-chain. J Immunol. 2005; 175(9):5975-80. DOI: 10.4049/jimmunol.175.9.5975. View

18.

Chatterjee M, Kis-Toth K, Thai T, Terhorst C, Tsokos G . SLAMF6-driven co-stimulation of human peripheral T cells is defective in SLE T cells. Autoimmunity. 2011; 44(3):211-8. PMC: 4465387. DOI: 10.3109/08916934.2010.530627. View

19.

Yasuda S, Stevens R, Terada T, Takeda M, Hashimoto T, Fukae J . Defective expression of Ras guanyl nucleotide-releasing protein 1 in a subset of patients with systemic lupus erythematosus. J Immunol. 2007; 179(7):4890-900. DOI: 10.4049/jimmunol.179.7.4890. View

20.

Koshy M, Berger D, Crow M . Increased expression of CD40 ligand on systemic lupus erythematosus lymphocytes. J Clin Invest. 1996; 98(3):826-37. PMC: 507493. DOI: 10.1172/JCI118855. View