title: Increased microRNA-323-3p in IL-22/IL-17-producing T cells and asthma: a role in the regulation of the TGF-β pathway and IL-22 production.
abstract: BACKGROUND
  IL-22- and IL-17-producing T cells have important roles in allergic diseases. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and modulate numerous biological processes. Little is known about the functions of miRNAs in IL-22/IL-17-producing T cells.
  
  
  METHODS
  IL-22- and IL-17-positive T cells were sorted from human peripheral blood mononuclear cells (PBMCs) by intracellular staining and dual-secretion assay. miRNA expression profiles were detected with TaqMan array microfluidic cards. T cells were transfected with miRNA mimics. Gene expression was analyzed using RT-qPCR and/or enzyme-linked immunosorbent assay in T-cell subsets and PBMCs from patients with asthma and atopic dermatitis.
  
  
  RESULTS
  The increased expression of miR-323-3p and noncoding RNA nc886 and reduced expression of miR-93, miR-181a, miR-26a, and miR-874 were detected in IL-22-producing T cells. The pathway analysis of the putative targets suggested that these differentially expressed miRNAs could impact the proliferation, differentiation, and effector functions of T cells. Further analyses showed the highest expression for miR-323-3p in IL-22- and IL-17-double-positive T cells and its capacity to suppress multiple genes from the transforming growth factor-β pathway and the production of IL-22 in T cells. An increased expression of miR-323-3p in PBMCs from patients with asthma and reverse correlation between miR-323-3p levels and IL-22 production in PBMCs cultured in T-cell growth conditions was observed.
  
  
  CONCLUSIONS
  Our data suggest that miR-323-3p acts in a negative feedback loop to control the production of IL-22 in IL-22/IL-17-producing T cells and might thus impact the T-cell responses in asthma.
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: J
authors.initials: J
authors.lastname: Kärner
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Wawrzyniak
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: S
authors.initials: S
authors.lastname: Tankov
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.|Institute of Molecular and Cellular Biology, University of Tartu, Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Runnel
authors.affiliation: Department of Obstetrics and Gynecology, Medical Faculty, University of Tartu and Competence Centre on Health Technologies, Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Aints
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Kisand
authors.affiliation: Department of Pulmonary Medicine, University of Tartu, Tartu, Estonia.|Lung Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Altraja
authors.affiliation: Department of Dermatology and Venereology, University of Tartu, Tartu, Estonia.|Dermatology Clinic, Tartu University Hospital, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Kingo
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: C A
authors.initials: CA
authors.lastname: Akdis
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Akdis
authors.affiliation: Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: A
authors.initials: A
authors.lastname: Rebane
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D020029:Base Pairing; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis*; D007378:Interleukins / Q000096:biosynthesis*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult; D000097043:Interleukin-22
chemical_list: D020381:Interleukin-17; D007378:Interleukins; D035683:MicroRNAs; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D016212:Transforming Growth Factor beta; D000097043:Interleukin-22; C573188:MIRN323 microRNA, human
keywords: 
  SMAD
  ; Th17 cell; Th22 cell; allergy; noncoding RNA