Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn's Disease Patients

Yuki Sekido, Yoshiaki Yasumizu, Junichi Nishimura, Hisako Kayama, Hiroshi Matsuno, Takayuki Ogino, Norikatsu Miyoshi, Hidekazu Takahashi, Naotsugu Haraguchi, Taishi Hata, Chu Matsuda, Yuichiro Doki, Masaki Mori, Kiyoshi Takeda, Naganari Ohkura, Shimon Sakaguchi, Tsunekazu Mizushima

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Abstract

Background/Aims: There is a heterogeneous subset innate myeloid cells, such as macrophages and dendritic cells, in the human intestinal lamina propria. Several studies have demonstrated that these cells contribute to the maintenance of gut homeostasis through the induction of inflammatory responses and tolerance via cell type-specific mechanisms; whereas, disrupted innate immune responses are implicated in the pathogenesis of Crohn's disease (CD). However, the detailed mechanisms by which each innate myeloid subset regulates gut homeostasis and inflammation largely remain unknown. We aimed to clarify the comprehensive gene expression profiles of innate myeloid cell -subsets in the lamina propria from normal human colons (NC) and the inflamed colon sites from patients with Crohn's disease (CDi). Methods: We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14-CD11c-, CD14-CD11c+, and CD14+CD11c+CD163low cells from NC and CDi. Results: Transcriptional analysis of the 3 subsets from the NC showed distinct gene expression patterns and gene ontology (GO) enrichment analysis revealed the associated innate myeloid subset-specific biological process (BP) terms. In addition, changes in gene expression patterns were observed in innate myeloid subsets from CDi. Furthermore, the core GO-BP terms for the genes upregulated in the innate myeloid cells from CDi were distinct from those found in NC. Conclusion: Our data identified the innate myeloid cell subset-specific transcriptomes and the associated enriched GO-BP terms in the NC and found these patterns were altered in CDi.

Original languageEnglish
Pages (from-to)194-204
Number of pages11
JournalDigestion
Volume99
Issue number3
DOIs
Publication statusPublished - Apr 1 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Gastroenterology

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    Sekido, Y., Yasumizu, Y., Nishimura, J., Kayama, H., Matsuno, H., Ogino, T., Miyoshi, N., Takahashi, H., Haraguchi, N., Hata, T., Matsuda, C., Doki, Y., Mori, M., Takeda, K., Ohkura, N., Sakaguchi, S., & Mizushima, T. (2019). Innate Myeloid Cell Subset-Specific Gene Expression Patterns in the Human Colon are Altered in Crohn's Disease Patients. Digestion, 99(3), 194-204. https://doi.org/10.1159/000490890