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The Role of PI3K Isoforms in Autoimmune Disease

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PI3K and AKT Isoforms in Immunity

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 436))

Abstract

Aberrant overactivation of the immune system can give rise to chronic and persistent self-attack, culminating in autoimmune disease. This is currently managed therapeutically using potent immunosuppressive and anti-inflammatory drugs. Class I phosphoinositide-3-kinases (PI3Ks) have been identified as ideal therapeutic targets for autoimmune diseases given their wide-ranging roles in immunological processes. Although progress has been hampered by issues such as poor drug tolerance and drug resistance, several PI3K inhibitors have now received regulatory approval with many others in development, including several intended to suppress the immune response in autoimmune and inflammatory diseases. This chapter reviews the evidence for contribution of aberrant PI3K activity to a range of autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and type I diabetes) and possible therapeutic application of isoform-specific PI3K inhibitors as immunosuppressive drugs.

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Abbreviations

APDS:

Activated PI3Kδ Syndrome

CNS:

Central nervous system

CIA:

Collagen-induced arthritis (CIA)

fMLP:

N-formylmethionyl-leucyl-phenylalanine

(h)TNFα:

Human tumour necrosis factor-α

MMPS:

Matrix metalloproteinases

MS:

Multiple sclerosis

mTORC2:

MTOR complex 2

NOD:

Non-obese diabetic

PDK-1:

Phosphoinositide-dependent kinase-1

PH:

pleckstrin homology

PI3K:

phosphoinositide-3-kinase

PIP2:

Phosphatidylinositol-(4,5)-bisphosphate

PIP3:

Phosphatidylinositol-(3,4,5)-trisphosphate

RA:

Rheumatoid arthritis

SLE:

Systemic lupus erythematosus

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  1. Department of Pharmacy and Pharmacology and Bath Centre for Therapeutic Innovation, University of Bath, Claverton Down, Bath, B2 7AY, UK

    Stephen G. Ward

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  1. Stephen G. Ward
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Correspondence to Stephen G. Ward .

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  1. Faculty of Medicine, Imperial College London, London, UK

    Margarita Dominguez-Villar

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Ward, S.G. (2022). The Role of PI3K Isoforms in Autoimmune Disease. In: Dominguez-Villar, M. (eds) PI3K and AKT Isoforms in Immunity . Current Topics in Microbiology and Immunology, vol 436. Springer, Cham. https://doi.org/10.1007/978-3-031-06566-8_14

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