title: Regulation of RORγt in Inflammatory Lymphoid Cell Differentiation.
abstract: T-helper 17 (Th17) cells differentiate from naïve CD4(+) T cells in response to signals from commensal microbiota and produce cytokines critical for the integrity of mucosal barriers. These cells also disseminate throughout the body, and are key participants in numerous inflammatory processes. A key challenge is to elucidate the mechanisms that govern Th17 cell beneficial versus pathogenic functions, characterized by different cytokine profiles. Mucosal Th17 cells require the nuclear hormone receptor RORγt for their differentiation in draining lymph nodes. Cytokine expression is enabled in select tissues, to which these cells migrate, by external cues, such as the serum amyloid A proteins produced in response to commensal bacteria by epithelial cells in the small intestine. Additional cell-intrinsic cues contributing to production of Th17 cytokines during both homeostasis and inflammation include the RORγt-associated DEAD-box RNA helicase DDX5 and long noncoding RNA (lncRNA) Rmrp. The helicase activity of DDX5 is required for Rmrp-mediated assembly of the complex and colocalization with RORγt throughout the genome to regulate key Th17 genes. How these are regulated in diverse microenvironments may provide insights for therapeutic intervention in autoimmune disease.
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016.
authors.forename: Wendy
authors.initials: W
authors.lastname: Huang
authors.affiliation: The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016 Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016.
authors.forename: Dan R
authors.initials: DR
authors.lastname: Littman
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D003463:Cues; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes; D038041:Lymphopoiesis / Q000235:genetics*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000378:metabolism; D058504:Th17 Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C544035:RMRP non-coding RNA, human; D062085:RNA, Long Noncoding; D000685:Serum Amyloid A Protein; C506749:Ddx5 protein, human; D053487:DEAD-box RNA Helicases