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Journal of Clinical Immunology

Erschienen in:

25.03.2019 | CME Review

Immune Dysregulation and Disease Pathogenesis due to Activating Mutations in PIK3CD—the Goldilocks’ Effect

verfasst von: Stuart G. Tangye, Julia Bier, Anthony Lau, Tina Nguyen, Gulbu Uzel, Elissa K. Deenick

Erschienen in: Journal of Clinical Immunology | Ausgabe 2/2019

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Abstract

“This porridge is too hot!” she exclaimed. So, she tasted the porridge from the second bowl. “This porridge is too cold,” she said. So, she tasted the last bowl of porridge. “Ahhh, this porridge is just right,” she said happily and she ate it all up. While this describes the adventures of Goldilocks in the classic fairytale “The Story of Goldilocks and the Three Bears,” it is an ideal analogy for the need for balanced signaling mediated by phosphatidylinositol-3-kinase (PI3K), a key signaling hub in immune cells. Either too little or too much PI3K activity is deleterious, even pathogenic—it needs to be “just right”! This has been elegantly demonstrated by the identification of inborn errors of immunity in key components of the PI3K pathway, and the impact of these mutations on immune regulation. Detailed analyses of patients with germline activating mutations in PIK3CD, as well as the parallel generation of novel murine models of this disease, have shed substantial light on the role of PI3K in lymphocyte development and differentiation, and mechanisms of disease pathogenesis resulting not only from PIK3CD mutations but genetic lesions in other components of the PI3K pathway. Furthermore, by being able to pharmacologically target PI3K, these monogenic conditions have provided opportunities for the implementation of precision medicine as a therapy, as well as to gain further insight into the consequences of modulating the PI3K pathway in clinical settings.

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Titel: Immune Dysregulation and Disease Pathogenesis due to Activating Mutations in PIK3CD—the Goldilocks’ Effect
verfasst von: Stuart G. Tangye
Julia Bier
Anthony Lau
Tina Nguyen
Gulbu Uzel
Elissa K. Deenick
Publikationsdatum: 25.03.2019
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 2/2019
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-019-00612-9

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