Skip to main content
. Author manuscript; available in PMC: 2025 Jan 1.
Published in final edited form as: J Allergy Clin Immunol Pract. 2023 Sep 28;12(1):69–78. doi: 10.1016/j.jaip.2023.09.016

Figure 1. PI3Kδ pathway in lymphocytes under physiological and pathological conditions.

Figure 1.

A) Under healthy physiological conditions, PI3Kδ activity in B and T cells is dynamically regulated during development and function, with periods of enhanced activity where FOXO and GSK3 are inhibited and mTOR signaling occurs and periods of dampened activity when mTOR is not activated and FOXO/GSK3 are disinhibited. Balanced PI3Kδ activity results in proper lymphocyte development and function.1–3 B) In APDS, PI3Kδ is hyperactive, resulting in excessive FOXO/GSK3 inhibition and mTOR activation. As a result, lymphocytes do not develop properly, with a general excess of immature or senescent cells and a deficit of functional cells. This deficiency and dysregulation create or contribute to the constellation of clinical manifestations, namely, infections, lymphoproliferation, autoimmunity, enteropathy, bronchiectasis, and an increased risk of malignancy, particularly lymphoma. Patients with APDS may also display neurological or cognitive symptoms, liver disease, and atopy. It is unclear whether some symptoms may be due to PI3Kδ expression in non-immune cells.5–9 Please note that PI3Kδ activity levels depicted are for illustrative purposes only and do not represent actual data. APDS indicates activated PI3Kδ syndrome; FOXO, forkhead box O; GSK3, glycogen synthase kinase-3; PI3Kδ, phosphoinositide 3-kinase δ.