@article{06ef0c17dd594ac8a5a5bd9c769c62b8,
title = "An IL-23R/IL-22 Circuit Regulates Epithelial Serum Amyloid A to Promote Local Effector Th17 Responses",
abstract = "RORγt+ Th17 cells are important for mucosal defenses but also contribute to autoimmune disease. They accumulate in the intestine in response to microbiota and produce IL-17 cytokines. Segmented filamentous bacteria (SFB) are Th17-inducing commensals that potentiate autoimmunity in mice. RORγt+ T cells were induced in mesenteric lymph nodes early after SFB colonization and distributed across different segments of the gastrointestinal tract. However, robust IL-17A production was restricted to the ileum, where SFB makes direct contact with the epithelium and induces serum amyloid A proteins 1 and 2 (SAA1/2), which promote local IL-17A expression in RORγt+ T cells. We identified an SFB-dependent role of type 3 innate lymphoid cells (ILC3), which secreted IL-22 that induced epithelial SAA production in a Stat3-dependent manner. This highlights the critical role of tissue microenvironment in activating effector functions of committed Th17 cells, which may have important implications for how these cells contribute to inflammatory disease.",
author = "Teruyuki Sano and Wendy Huang and Hall, {Jason A.} and Yi Yang and Alessandra Chen and Gavzy, {Samuel J.} and Lee, {June Yong} and Ziel, {Joshua W.} and Miraldi, {Emily R.} and Domingos, {Ana I.} and Richard Bonneau and Littman, {Dan R.}",
note = "Funding Information: We thank Sebastian Amigorena, Kenneth Cadwell, Suzan R. Schwab, and Sang V. Kim for valuable discussion, Wenjun Ouyang for providing control and anti-IL-22 neutralizing antibody, Jeffrey M. Friedman for the EF1-lox-stop-lox-GFP-L10 mice, and Frederick De Beer for providing the Saa mutant mice. We thank Maria Ciofani for her contributions to the RNA-seq studies. We thank Richard M. Myers at HudsonAlpha Institute for Biotechnology for RNA-seq and TRAP-seq studies. This work was supported by fellowships from the TOYOBO Bioscience foundation (T.S.), Human Frontier Science Program (T.S.), Cancer Research Institute (W.H.), and NIH T32 CA009161_Levy (W.H.), and Dale and Betty Frey Fellowship of the Damon Runyon Cancer Research Foundation 2105-12 (J.A.H); and by the Howard Hughes Medical Institute (D.R.L.), the Helen and Martin Kimmel Center for Biology and Medicine (D.R.L.), and National Institutes of Health grant R01DK103358 (R.B. and D.R.L.). Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",
year = "2015",
month = oct,
day = "8",
doi = "10.1016/j.cell.2015.08.061",
language = "English (US)",
volume = "163",
pages = "381--393",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}