The human long noncoding <scp>RNA</scp> lnc‐<scp>IL</scp>7<scp>R</scp> regulates the inflammatory response

<jats:p>Long noncoding <jats:styled-content style="fixed-case">RNA</jats:styled-content>s (lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content>s), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, there is not much knowledge regarding their roles in the inflammatory response. In this study, we performed human lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content> microarray assays and identified a number of lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content>s that demonstrated altered expression in response to <jats:styled-content style="fixed-case">LPS</jats:styled-content> stimulation. Of these lnc<jats:styled-content style="fixed-case">RNA</jats:styled-content>s, lnc‐<jats:styled-content style="fixed-case">IL</jats:styled-content>7<jats:styled-content style="fixed-case">R</jats:styled-content>, which overlaps with the 3′untranslated region (3′<jats:styled-content style="fixed-case">UTR</jats:styled-content>) of the human interleukin‐7 receptor α‐subunit gene <jats:italic>(IL7R)</jats:italic> gene, was significantly upregulated in <jats:styled-content style="fixed-case">LPS</jats:styled-content>‐treated cells. Functionally, lnc‐IL7R was capable of diminishing the <jats:styled-content style="fixed-case">LPS</jats:styled-content>‐induced inflammatory response, demonstrated by elevated expression of <jats:styled-content style="fixed-case">LPS</jats:styled-content>‐induced <jats:styled-content style="fixed-case">E</jats:styled-content>‐selectin, <jats:styled-content style="fixed-case">VCAM</jats:styled-content>‐1, <jats:styled-content style="fixed-case">IL</jats:styled-content>‐6, and <jats:styled-content style="fixed-case">IL</jats:styled-content>‐8 in lnc‐<jats:styled-content style="fixed-case">IL</jats:styled-content>7<jats:styled-content style="fixed-case">R</jats:styled-content> knockdown cells. Mechanistically, we found that lnc‐<jats:styled-content style="fixed-case">IL</jats:styled-content>7<jats:styled-content style="fixed-case">R</jats:styled-content> knockdown diminished trimethylation of histone H3 at lysine 27 (H3K27me3), a hallmark of silent transcription, at the proximal promoters of the inflammatory mediators. Our data suggest that lnc‐IL7R contributes another layer of complexity in regulation of the inflammatory response.</jats:p>