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Decline of miR‐124 in myeloid cells promotes regulatory T‐cell development in hepatitis C virus infection
Author(s) -
Ren Jun P.,
Wang Lin,
Zhao Juan,
Wang Ling,
Ning Shun B.,
El Gazzar Mohamed,
Moorman Jonathan P.,
Yao Zhi Q.
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12680
Subject(s) - foxp3 , stat protein , immune system , myeloid derived suppressor cell , immunology , biology , gene silencing , myeloid , hepatitis c virus , chronic infection , rna , virology , virus , cancer research , stat3 , suppressor , signal transduction , gene , microbiology and biotechnology , biochemistry
Summary Myeloid‐derived suppressor cells ( MDSC s) and micro RNA s (mi RNA s) contribute to attenuating immune responses during chronic viral infection; however, the precise mechanisms underlying their suppressive activities remain incompletely understood. We have recently shown marked expansion of MDSC s that promote regulatory T (Treg) cell development in patients with chronic hepatitis C virus ( HCV ) infection. Here we further investigated whether the HCV ‐induced expansion of MDSC s and Treg cells is regulated by an mi RNA ‐mediated mechanism. The RNA array analysis revealed that six mi RNA s were up‐regulated and six mi RNA s were down‐regulated significantly in myeloid cells during HCV infection. Real‐time RT ‐ PCR confirmed the down‐regulation of miR‐124 in MDSC s from HCV patients. Bioinformatic analysis suggested that miR‐124 may be involved in the regulation of signal transducer and activator of transcription 3 ( STAT ‐3), which was overexpressed in MDSC s from HCV patients. Notably, silencing of STAT ‐3 significantly increased the miR‐124 expression, whereas reconstituting miR‐124 decreased the levels of STAT ‐3, as well as interleukin‐10 and transforming growth factor‐ β , which were overexpressed in MDCS s, and reduced the frequencies of Foxp3 + Treg cells that were developed during chronic HCV infection. These results suggest that reciprocal regulation of miR‐124 and STAT ‐3 in MDSC s promotes Treg cell development, thus uncovering a novel mechanism for the expansion of MDSC and Treg cells during HCV infection.