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.
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Sano
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Wendy
authors.initials: W
authors.lastname: Huang
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Hall
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; The Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Chen
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Gavzy
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: June-Yong
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Ziel
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, NY 10003, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Miraldi
authors.affiliation: Obesity Laboratory, Instituto Gulbenkian de Ciência, Oeiras 2780-156, Portugal.
authors.forename: Ana I
authors.initials: AI
authors.lastname: Domingos
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, Computer Science Department, New York University, New York, NY 10003, USA; Simons Center for Data Analysis, Simons Foundation, New York, NY 10010, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.affiliation: Molecular Pathogenesis Program, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA; The Howard Hughes Medical Institute, New York University School of Medicine, New York, NY 10016, USA. Electronic address: dan.littman@med.nyu.edu.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
mesh_terms: D000818:Animals; D000069196:Gastrointestinal Microbiome; D007113:Immunity, Innate; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D007422:Intestines / Q000033:anatomy & histology / Q000276:immunology* / Q000382:microbiology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018123:Receptors, Interleukin / Q000276:immunology / Q000378:metabolism*; D000685:Serum Amyloid A Protein / Q000378:metabolism*; D015398:Signal Transduction; D058504:Th17 Cells / Q000276:immunology*; D000097043:Interleukin-22
chemical_list: D007378:Interleukins; D018123:Receptors, Interleukin; D000685:Serum Amyloid A Protein; D000097043:Interleukin-22; C489995:Saa2 protein, mouse; C528688:interleukin-23 receptor, mouse