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Increased micro RNA ‐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
Author(s) -
Kärner J.,
Wawrzyniak M.,
Tankov S.,
Runnel T.,
Aints A.,
Kisand K.,
Altraja A.,
Kingo K.,
Akdis C. A.,
Akdis M.,
Rebane A.
Publication year - 2017
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.12907
Subject(s) - microrna , asthma , medicine , transforming growth factor , immunology , allergy , interleukin 4 , cytokine , biology , genetics , gene
Abstract Background IL ‐22‐ and IL ‐17‐producing T cells have important roles in allergic diseases. Micro RNA s (mi RNA s) are posttranscriptional regulators of gene expression and modulate numerous biological processes. Little is known about the functions of mi RNA s 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 ( PBMC s) by intracellular staining and dual‐secretion assay. mi RNA expression profiles were detected with TaqMan array microfluidic cards. T cells were transfected with mi RNA mimics. Gene expression was analyzed using RT ‐ qPCR and/or enzyme‐linked immunosorbent assay in T‐cell subsets and PBMC s 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 mi RNA s 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 PBMC s from patients with asthma and reverse correlation between miR‐323‐3p levels and IL ‐22 production in PBMC s 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.