Characterization of T-cell receptor repertoire in inflamed tissues of patients with Crohn's disease through deep sequencing

Christopher G. Chapman, Rui Yamaguchi, Kenji Tamura, Jerome Weidner, Seiya Imoto, John Kwon, Hua Fang, Poh Yin Yew, Susana R. Marino, Satoru Miyano, Yusuke Nakamura, Kazuma Kiyotani

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Intestinal tissues of patients with Crohn's disease (CD) contain expanded populations of T cells which are believed to mediate inflammation. We performed a detailed characterization of these T-cell repertoires. Methods: We obtained biopsies from the neoterminal ileum of 12 patients undergoing evaluation for postoperative recurrent CD and 4 individuals with normal terminal ileum and no history of inflammatory bowel disease (controls). Samples of diseased terminal ileum were obtained from 5 patients undergoing surgery for stricturing or penetrating CD. Total RNA was extracted from tissues and peripheral blood mononuclear cells, and cDNAs were generated. We used next-generation sequencing to characterize T-cell receptor (TCR)-α and TCR-β cDNAs in ileal mucosal tissue and matched peripheral blood mononuclear cells of 17 patients with CD to identify oligoclonal expansions of T-cell populations associated with CD. Results: TCR diversity in mucosal tissue was significantly lower than that of matched peripheral blood mononuclear cells, indicating expansion of certain T-cell populations in inflamed intestinal tissue. A single TCR-β clonotype, CASSWTNGEQYF (TRBV10-1-TRBJ2-7), was enriched at a frequency of 7.0% to 28.9% in the neoterminal ileum of 4 of 12 patients with recurrent CD. The abundance of this clonotype significantly correlated with the severity of disease recurrence, based on Rutgeerts score (P 0.015). Conclusions: Specific populations of T cells are expanded in the inflamed intestinal mucosa of patients with CD; their abundance correlates with severity of disease recurrence. Studies of these T cells could provide information about mechanisms of CD pathogenesis. Deep TCR sequencing is a powerful tool that rapidly provides in-depth, real-time assessment of the T-cell repertoire.

Original languageEnglish (US)
Pages (from-to)1275-1285
Number of pages11
JournalInflammatory Bowel Diseases
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2016

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High-Throughput Nucleotide Sequencing
T-Cell Antigen Receptor
Crohn Disease
T-Lymphocytes
Ileum
Blood Cells
Population
Mucous Membrane
Complementary DNA
Recurrence
Intestinal Mucosa
Inflammatory Bowel Diseases
RNA
Inflammation
Biopsy

Keywords

  • genetic
  • IBD
  • immune regulation
  • inflammatory bowel diseases
  • NGS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Characterization of T-cell receptor repertoire in inflamed tissues of patients with Crohn's disease through deep sequencing. / Chapman, Christopher G.; Yamaguchi, Rui; Tamura, Kenji; Weidner, Jerome; Imoto, Seiya; Kwon, John; Fang, Hua; Yew, Poh Yin; Marino, Susana R.; Miyano, Satoru; Nakamura, Yusuke; Kiyotani, Kazuma.

In: Inflammatory Bowel Diseases, Vol. 22, No. 6, 01.06.2016, p. 1275-1285.

Research output: Contribution to journalArticle

Chapman, CG, Yamaguchi, R, Tamura, K, Weidner, J, Imoto, S, Kwon, J, Fang, H, Yew, PY, Marino, SR, Miyano, S, Nakamura, Y & Kiyotani, K 2016, 'Characterization of T-cell receptor repertoire in inflamed tissues of patients with Crohn's disease through deep sequencing', Inflammatory Bowel Diseases, vol. 22, no. 6, pp. 1275-1285. https://doi.org/10.1097/MIB.0000000000000752
Chapman, Christopher G. ; Yamaguchi, Rui ; Tamura, Kenji ; Weidner, Jerome ; Imoto, Seiya ; Kwon, John ; Fang, Hua ; Yew, Poh Yin ; Marino, Susana R. ; Miyano, Satoru ; Nakamura, Yusuke ; Kiyotani, Kazuma. / Characterization of T-cell receptor repertoire in inflamed tissues of patients with Crohn's disease through deep sequencing. In: Inflammatory Bowel Diseases. 2016 ; Vol. 22, No. 6. pp. 1275-1285.
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abstract = "Background: Intestinal tissues of patients with Crohn's disease (CD) contain expanded populations of T cells which are believed to mediate inflammation. We performed a detailed characterization of these T-cell repertoires. Methods: We obtained biopsies from the neoterminal ileum of 12 patients undergoing evaluation for postoperative recurrent CD and 4 individuals with normal terminal ileum and no history of inflammatory bowel disease (controls). Samples of diseased terminal ileum were obtained from 5 patients undergoing surgery for stricturing or penetrating CD. Total RNA was extracted from tissues and peripheral blood mononuclear cells, and cDNAs were generated. We used next-generation sequencing to characterize T-cell receptor (TCR)-α and TCR-β cDNAs in ileal mucosal tissue and matched peripheral blood mononuclear cells of 17 patients with CD to identify oligoclonal expansions of T-cell populations associated with CD. Results: TCR diversity in mucosal tissue was significantly lower than that of matched peripheral blood mononuclear cells, indicating expansion of certain T-cell populations in inflamed intestinal tissue. A single TCR-β clonotype, CASSWTNGEQYF (TRBV10-1-TRBJ2-7), was enriched at a frequency of 7.0{\%} to 28.9{\%} in the neoterminal ileum of 4 of 12 patients with recurrent CD. The abundance of this clonotype significantly correlated with the severity of disease recurrence, based on Rutgeerts score (P 0.015). Conclusions: Specific populations of T cells are expanded in the inflamed intestinal mucosa of patients with CD; their abundance correlates with severity of disease recurrence. Studies of these T cells could provide information about mechanisms of CD pathogenesis. Deep TCR sequencing is a powerful tool that rapidly provides in-depth, real-time assessment of the T-cell repertoire.",
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AU - Chapman, Christopher G.

AU - Yamaguchi, Rui

AU - Tamura, Kenji

AU - Weidner, Jerome

AU - Imoto, Seiya

AU - Kwon, John

AU - Fang, Hua

AU - Yew, Poh Yin

AU - Marino, Susana R.

AU - Miyano, Satoru

AU - Nakamura, Yusuke

AU - Kiyotani, Kazuma

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Y1 - 2016/6/1

N2 - Background: Intestinal tissues of patients with Crohn's disease (CD) contain expanded populations of T cells which are believed to mediate inflammation. We performed a detailed characterization of these T-cell repertoires. Methods: We obtained biopsies from the neoterminal ileum of 12 patients undergoing evaluation for postoperative recurrent CD and 4 individuals with normal terminal ileum and no history of inflammatory bowel disease (controls). Samples of diseased terminal ileum were obtained from 5 patients undergoing surgery for stricturing or penetrating CD. Total RNA was extracted from tissues and peripheral blood mononuclear cells, and cDNAs were generated. We used next-generation sequencing to characterize T-cell receptor (TCR)-α and TCR-β cDNAs in ileal mucosal tissue and matched peripheral blood mononuclear cells of 17 patients with CD to identify oligoclonal expansions of T-cell populations associated with CD. Results: TCR diversity in mucosal tissue was significantly lower than that of matched peripheral blood mononuclear cells, indicating expansion of certain T-cell populations in inflamed intestinal tissue. A single TCR-β clonotype, CASSWTNGEQYF (TRBV10-1-TRBJ2-7), was enriched at a frequency of 7.0% to 28.9% in the neoterminal ileum of 4 of 12 patients with recurrent CD. The abundance of this clonotype significantly correlated with the severity of disease recurrence, based on Rutgeerts score (P 0.015). Conclusions: Specific populations of T cells are expanded in the inflamed intestinal mucosa of patients with CD; their abundance correlates with severity of disease recurrence. Studies of these T cells could provide information about mechanisms of CD pathogenesis. Deep TCR sequencing is a powerful tool that rapidly provides in-depth, real-time assessment of the T-cell repertoire.

AB - Background: Intestinal tissues of patients with Crohn's disease (CD) contain expanded populations of T cells which are believed to mediate inflammation. We performed a detailed characterization of these T-cell repertoires. Methods: We obtained biopsies from the neoterminal ileum of 12 patients undergoing evaluation for postoperative recurrent CD and 4 individuals with normal terminal ileum and no history of inflammatory bowel disease (controls). Samples of diseased terminal ileum were obtained from 5 patients undergoing surgery for stricturing or penetrating CD. Total RNA was extracted from tissues and peripheral blood mononuclear cells, and cDNAs were generated. We used next-generation sequencing to characterize T-cell receptor (TCR)-α and TCR-β cDNAs in ileal mucosal tissue and matched peripheral blood mononuclear cells of 17 patients with CD to identify oligoclonal expansions of T-cell populations associated with CD. Results: TCR diversity in mucosal tissue was significantly lower than that of matched peripheral blood mononuclear cells, indicating expansion of certain T-cell populations in inflamed intestinal tissue. A single TCR-β clonotype, CASSWTNGEQYF (TRBV10-1-TRBJ2-7), was enriched at a frequency of 7.0% to 28.9% in the neoterminal ileum of 4 of 12 patients with recurrent CD. The abundance of this clonotype significantly correlated with the severity of disease recurrence, based on Rutgeerts score (P 0.015). Conclusions: Specific populations of T cells are expanded in the inflamed intestinal mucosa of patients with CD; their abundance correlates with severity of disease recurrence. Studies of these T cells could provide information about mechanisms of CD pathogenesis. Deep TCR sequencing is a powerful tool that rapidly provides in-depth, real-time assessment of the T-cell repertoire.

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KW - immune regulation

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