title: Characterization of T-cell Receptor Repertoire in Inflamed Tissues of Patients with Crohn's Disease Through Deep Sequencing.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: *Section of Gastroenterology, Department of Medicine, The University of Chicago, Chicago, Illinois; †Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan; ‡Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, Illinois; and §Department of Pathology, The University of Chicago, Chicago, Illinois.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Chapman
authors.forename: Rui
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Jerome
authors.initials: J
authors.lastname: Weidner
authors.forename: Seiya
authors.initials: S
authors.lastname: Imoto
authors.forename: John
authors.initials: J
authors.lastname: Kwon
authors.forename: Hua
authors.initials: H
authors.lastname: Fang
authors.forename: Poh Yin
authors.initials: PY
authors.lastname: Yew
authors.forename: Susana R
authors.initials: SR
authors.lastname: Marino
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012313:RNA / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012008:Recurrence; D012720:Severity of Illness Index; D013601:T-Lymphocytes / Q000378:metabolism*; D055815:Young Adult
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D012313:RNA