Deregulation of long intergenic non-coding RNAs in CD4+ T cells of lamina propria in Crohn's disease through transcriptome profiling

Manuel B. Braga-Neto, Joseph M. Gaballa, Adebowale O. Bamidele, Olga F. Sarmento, Phyllis Svingen, Michelle Gonzalez, Guilherme Piovezani Ramos, Mary R. Sagstetter, Sayed Obaidullah Aseem, Zhifu Sun, William A. Faubion

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background: The aetiology of Crohn's disease [CD] involves immune dysregulation in a genetically susceptible individual. Genome-wide association studies [GWAS] have identified 200 loci associated with CD, ulcerative colitis, or both, most of which fall within non-coding DNA regions. Long non-coding RNAs [lncRNAs] regulate gene expression by diverse mechanisms and have been associated with disease activity in inflammatory bowel disease. However, disease-associated lncRNAs have not been characterised in pathogenic immune cell populations. Methods: Terminal ileal samples were obtained from 22 CD patients and 13 controls. RNA from lamina propria CD4+ T cells was sequenced and long intergenic non-coding RNAs [lincRNAs] were detected. Overall expression patterns, differential expression [DE], and pathway and gene enrichment analyses were performed. Knockdown of novel lincRNAs XLOC-000261 and XLOC-000014 was performed. Expression of Th1 or Th17-associated transcription factors, T-bet and RORγt, respectively, was assessed by flow cytometry. Results: A total of 6402 lincRNAs were expressed, 960 of which were novel. Unsupervised clustering and principal component analysis showed that the lincRNA expression discriminated patients from controls. A total of 1792 lincRNAs were DE, and 295 [79 novel; 216 known] mapped to 267 of 5727 DE protein-coding genes. The novel lincRNAs were enriched in inflammatory and Notch signalling pathways [p <0.05]. Furthermore, DE lincRNAs in CD patients were more frequently found in DNA regions with known inflammatory bowel disease [IBD]-associated loci. The novel lincRNA XLOC-000261 negatively regulated RORγt expression in Th17 cells. Conclusions: We describe a novel set of DE lincRNAs in CD-associated CD4+ cells and demonstrate that novel lincRNA XLOC-000261 appears to negatively regulate RORγt protein expression in Th17 cells.

Original languageEnglish (US)
Pages (from-to)96-109
Number of pages14
JournalJournal of Crohn's and Colitis
Volume14
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Crohn's disease
  • inflammation
  • long non-coding RNA

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Deregulation of long intergenic non-coding RNAs in CD4<sup>+</sup> T cells of lamina propria in Crohn's disease through transcriptome profiling'. Together they form a unique fingerprint.

  • Cite this

    Braga-Neto, M. B., Gaballa, J. M., Bamidele, A. O., Sarmento, O. F., Svingen, P., Gonzalez, M., Ramos, G. P., Sagstetter, M. R., Aseem, S. O., Sun, Z., & Faubion, W. A. (2020). Deregulation of long intergenic non-coding RNAs in CD4+ T cells of lamina propria in Crohn's disease through transcriptome profiling. Journal of Crohn's and Colitis, 14(1), 96-109. https://doi.org/10.1093/ecco-jcc/jjz109