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The Therapeutic Potential for PI3K Inhibitors in Autoimmune Rheumatic Diseases.

Published version
Peer-reviewed

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Type

Article

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Authors

Banham-Hall, Edward 
Clatworthy, Menna R 

Abstract

The class 1 PI3Ks are lipid kinases with key roles in cell surface receptor-triggered signal transduction pathways. Two isoforms of the catalytic subunits, p110γ and p110δ, are enriched in leucocytes in which they promote activation, cellular growth, proliferation, differentiation and survival through the generation of the second messenger PIP3. Genetic inactivation or pharmaceutical inhibition of these PI3K isoforms in mice result in impaired immune responses and reduced susceptibility to autoimmune and inflammatory conditions. We review the PI3K signal transduction pathways and the effects of inhibition of p110γ and/or p110δ on innate and adaptive immunity. Focusing on rheumatoid arthritis and systemic lupus erythematosus we discuss the preclinical evidence and prospects for small molecule inhibitors of p110γ and/or p110δ in autoimmune disease.

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Keywords

PI3K inhibitors, PI3K., autoimmunity, humoral immune, pleckstrin homology, rheumatoid arthritis, systemic lupus erythematosus

Journal Title

Open Rheumatol J

Conference Name

Journal ISSN

1874-3129
1874-3129

Volume Title

6

Publisher

Bentham Science Publishers Ltd.