Innate PI3K p110δ Regulates Th1/Th17 Development and Microbiota-Dependent Colitis

• Published in: The Journal of immunology (1950) Vol. 192; no. 8; pp. 3958 - 3968
• Main Authors: Steinbach, Erin C, Kobayashi, Taku, Russo, Steven M, Sheikh, Shehzad Z, Gipson, Gregory R, Kennedy, Samantha T, Uno, Jennifer K, Mishima, Yoshiyuki, Borst, Luke B, Liu, Bo, Herfarth, Hans, Ting, Jenny P Y, Sartor, R Balfour, Plevy, Scott E
• Format: Journal Article
• Language: English
• Published: United States 15.04.2014
• Subjects: Animals; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Class Ia Phosphatidylinositol 3-Kinase - genetics; Class Ia Phosphatidylinositol 3-Kinase - metabolism; Colitis - genetics; Colitis - immunology; Colitis - metabolism; Colitis - microbiology; Colitis - pathology; Cytokines - biosynthesis; Disease Models, Animal; Gene Expression Regulation; Immunity, Innate - genetics; Interleukin-10 - biosynthesis; Intestinal Mucosa - immunology; Intestinal Mucosa - metabolism; Intestinal Mucosa - microbiology; Intestinal Mucosa - pathology; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Knockout; Microbiota; Th1 Cells - immunology; Th1 Cells - metabolism; Th17 Cells - immunology; Th17 Cells - metabolism; TOR Serine-Threonine Kinases - metabolism

The p110δ subunit of class IA PI3K modulates signaling in innate immune cells. We previously demonstrated that mice harboring a kinase-dead p110δ subunit (p110δKD) develop spontaneous colitis. Macrophages contributed to the Th1/Th17 cytokine bias in p110δKD mice through increased IL-12 and IL-23 exp...