title: MicroRNA-205 Maintains T Cell Development following Stress by Regulating Forkhead Box N1 and Selected Chemokines.
abstract: The thymus, an organ responsible for T cell development, is one of the more stress-sensitive tissues in the body. Stress, in the form of infections, radiation exposure, and steroids, impairs thymic epithelial cell (TEC) functions and induces the programmed cell death of immature thymocytes. MicroRNAs are small noncoding RNAs involved in tissue repair and homeostasis, with several supporting T cell development. We report that miR-205, an epithelial-specific miR, maintains thymopoiesis following inflammatory perturbations. Thus, the activation of diverse pattern recognition receptors in mice causes a more severe thymic hypoplasia and delayed T cell recovery when miR-205 is conditionally ablated in TECs. Gene expression comparisons in the TECs with/without miR-205 revealed a significant differential regulation of chemokine/chemokine receptor pathways, antigen processing components, and changes in the Wnt signaling system. This was partly a consequence of reduced expression of the transcriptional regulator of epithelial cell function, Forkhead Box N1 (Foxn1), and its two regulated targets, stem cell factor and ccl25, following stress. miR-205 mimics supplemented into miR-205-deficient fetal thymic organ cultures restored Foxn1 expression along with ccl25 and stem cell factor A number of putative targets of miR-205 were up-regulated in TECs lacking miR-205, consistent with an important role for this miR in supporting T cell development in response to stress.
authors.affiliation: From the Departments of Immunology.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Hoover
authors.affiliation: From the Departments of Immunology.
authors.forename: Igor
authors.initials: I
authors.lastname: Dozmorov
authors.affiliation: From the Departments of Immunology.
authors.forename: Jessica
authors.initials: J
authors.lastname: MacLeod
authors.affiliation: From the Departments of Immunology.
authors.forename: Qiumei
authors.initials: Q
authors.lastname: Du
authors.affiliation: Pediatrics.|Internal Medicine.|Children's Health, Dallas, Texas 75235.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: de la Morena
authors.affiliation: Internal Medicine.|Children's Health, Dallas, Texas 75235.
authors.forename: Joseph
authors.initials: J
authors.lastname: Forbess
authors.affiliation: Internal Medicine.|Children's Health, Dallas, Texas 75235.
authors.forename: Kristine
authors.initials: K
authors.lastname: Guleserian
authors.affiliation: Molecular Biology, and.
authors.forename: Ondine B
authors.initials: OB
authors.lastname: Cleaver
authors.affiliation: From the Departments of Immunology, nicolai.vanoers@utsouthwestern.edu.|Pediatrics.|Microbiology, The University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9093 and.
authors.forename: Nicolai S C
authors.initials: NS
authors.lastname: van Oers
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000235:genetics / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
chemical_list: C491541:Ccl25 protein, mouse; D019742:Chemokines, CC; D051858:Forkhead Transcription Factors; C576666:MIRN205 microRNA, mouse; D035683:MicroRNAs; D019089:Stem Cell Factor; C090140:Whn protein
keywords: T-cell biology; development; lipopolysaccharide (LPS); microRNA (miRNA); pathogen-associated molecular pattern (PAMP); pattern recognition receptor (PRR); stress; stress response