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

• Published in: Allergy (Copenhagen) Vol. 72; no. 1; pp. 55 - 65
• Main Authors: Kärner, J., Wawrzyniak, M., Tankov, S., Runnel, T., Aints, A., Kisand, K., Altraja, A., Kingo, K., Akdis, C. A., Akdis, M., Rebane, A.
• Format: Journal Article
• Language: English
• Published: Denmark 01.01.2017
• Subjects: Adult; allergy; Asthma - diagnosis; Asthma - genetics; Asthma - immunology; Asthma - metabolism; Base Pairing; Cluster Analysis; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-17 - biosynthesis; Interleukin-22; Interleukins - biosynthesis; MicroRNAs - chemistry; MicroRNAs - genetics; Middle Aged; noncoding RNA; RNA, Messenger - chemistry; RNA, Messenger - genetics; Signal Transduction; SMAD; STAT3 Transcription Factor - metabolism; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Th17 cell; Th22 cell; Transforming Growth Factor beta - metabolism; Young Adult; allergy; noncoding RNA; SMAD; Th17 cell; Th22 cell
• ISSN: 0105-4538; 1398-9995
• DOI: 10.1111/all.12907

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. Material and 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.