Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 7; Issue 29; 20 December 2005 Abstract
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Immune disorders associated with T-cell signalling

Beverley Wilkinson, Jocelyn S. Downey and Christopher E. Rudd

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Figure 5. Immune disorders associated with T-cell signalling. Depiction of the various disease states have been connected to signalling proteins in T cells. Mutations in CD45 or altered CD45 expression have been linked to SCID, HIV-1 infectivity and systemic lupus erythematosus (SLE)-like syndome. Mutations in PTPN22 (LYP/PEP) confer a predisposition to a range of autoimmune diseases such as rheumatoid arthritis (RA), type 1 diabetes, SLE, Graves’ disease and Hashimoto thyroiditis. Loss of ZAP-70 expression causes severe combined immunodeficiency (SCID), while mutations in the kinase have been linked to a SCID-like syndrome as well as the onset of murine rheumatoid arthritis (RA). The loss of ubiquitin E3 ligases (Cbl-b, GRAIL, Itch and Nedd-4) can cause spontaneous autoimmunity as a result of an inability to degrade key signalling proteins. Mouse models have implicated the adaptor LAT in the development of RA, whereas loss of WASP expression has been causally linked to Wiscott–Aldrich syndrome (WAS) and X-linked severe congenital neutropenia (XLN). SLAM/SAP signalling defects are responsible for the development of X-linked lymphoproliferative disorder (XLP) in humans, while mutations in JAKs have been causally connected to the development of SCID via defects in cytokine signalling. Lastly, altered Smad signalling via TGF-b signalling has been linked to the onset of an inflammatory bowel disease (IBD)-like disorder in mice. Abbreviations: ADAP, adhesion-and degranulation-promoting protein; GADS, Grb2-related adaptor downstream of Shc; JAK, Janus kinase; NCK, noncatalytic region of tyrosine kinase adaptor protein 1; PLCg1, phospholipase Cg1; PTPN22, protein tyrosine phosphatase, non-receptor type 22; SAP, SLAM-associated protein; SH2, Src-homology 2; SKAP-55, Src-family-kinase-associated phosphoprotein of 55 kDa; SLP-76, SH2-domain-containing leukocyte protein of 76 kDa; SLAM, signalling lymphocyte activation molecule; STAT, signal transducer and activators of transcription; TCR, T-cell receptor; TGF-b, transforming growth factor b; VASP, vasodilator-stimulated phosphoprotein; WASP, Wiskott Aldrich syndrome protein; ZAP-70, zeta-associated protein 70.

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