J. Thauland, Timothy Pellerin, Laurence Ohgami, Robert S. Bacchetta, Rosa Butte, Manish J. Image_2_Case Study: Mechanism for Increased Follicular Helper T Cell Development in Activated PI3K Delta Syndrome.TIFF <p>Gain-of-function variants in p110δ, the catalytic subunit of phosphatidylinositol 3-kinase (PI3K) expressed in lymphocytes, cause activated PI3-kinase δ syndrome (APDS), a primary immunodeficiency that is characterized by recurrent infections, viremia, lymphadenopathy, and autoimmunity. The mechanism of autoimmunity in APDS has not been well-understood. Here, we show the profound skewing of peripheral CD4<sup>+</sup> T cells to a T follicular helper (T<sub>FH</sub>) phenotype in a patient with APDS bearing a novel p110δ variant, Y524S. We also saw a diminishment of transient Foxp3 expression in activated T cells. Mechanistic studies revealed that both the new variant and a previously described, pathogenic variant (E81K) enhanced an interaction between intracellular Osteopontin and p85α. This interaction had been shown in mice to promote T<sub>FH</sub> differentiation. Our results demonstrate a new influence of PI3K on human T cell differentiation that is unrelated to its lipid-kinase activity and suggest that T<sub>FH</sub> should be monitored in APDS patients.</p> primary immunodeficiency;activated PI3K delta syndrome (APDS);PI3K;T follicular helper cells;osteopontin 2019-04-12
    https://frontiersin.figshare.com/articles/figure/Image_2_Case_Study_Mechanism_for_Increased_Follicular_Helper_T_Cell_Development_in_Activated_PI3K_Delta_Syndrome_TIFF/7987235
10.3389/fimmu.2019.00753.s002