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HUMORAL IMMUNITY

PI3Kδ: Too much of a good thing

Nature Immunology volume 19, pages 910–911 (2018)Cite this article

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PI3Kδ regulates adaptive immune thresholds and limits immunity to endogenous microbiota.

Activating mutations in the p110δ subunit of phosphatidylinositol-3-OH kinase (PI3Kδ) are associated with two related immunodeficiency syndromes, PASLI (p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency) and APDS (activated PI3Kδ syndrome). In this issue of Nature Immunology, Preite et al.1 develop a mouse model expressing PI3Kδ with a common activating mutation (PI3KδE1020K; hereafter referred to as PI3Kδ*) that recapitulates many essential features of the human syndromes. They clearly demonstrate the pathogenic role of activated PI3Kδ, providing a compelling rationale for ongoing clinical trials of PI3Kδ inhibitors in PASLI and APDS2. Furthermore, the investigators provide insights into why adaptive immunity is both exuberant and ineffective in PASLI and APDS. Surprisingly, this involves a critical role for PI3Kδ in controlling immune responses to the microbiome.

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Fig. 1: PI3Kδ regulates lymphocyte activation.

References

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  1. Department of Medicine, Section of Rheumatology, Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, IL, USA

    Domenick E. Kennedy & Marcus R. Clark

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  1. Domenick E. Kennedy
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  2. Marcus R. Clark
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Correspondence to Marcus R. Clark.

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The authors declare no competing interests.

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Kennedy, D.E., Clark, M.R. PI3Kδ: Too much of a good thing. Nat Immunol 19, 910–911 (2018). https://doi.org/10.1038/s41590-018-0183-2

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  • DOI: https://doi.org/10.1038/s41590-018-0183-2

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