AUTHOR=Hong Sung Noh , Park Joo-Young , Yang So-Yun , Lee Chansu , Kim Young-Ho , Joung Je-Gun 

TITLE=Reduced diversity of intestinal T-cell receptor repertoire in patients with Crohn’s disease

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.932373

DOI=10.3389/fcimb.2022.932373

ISSN=2235-2988

ABSTRACT=Background: Intestinal micro-environment directly determines the human T-cell receptor (TCR) repertoire. Despite its extreme diversity, TCR repertoire analysis may provide a better understanding of the immune system in patients with inflammatory bowel disease. 
Methods: To investigate TCR repertoires in the intestinal mucosa, RNA sequencing was performed on the inflamed and non-inflamed intestinal mucosa obtained from the 13 patients with Crohn’s disease (CD), and healthy mucosa from 9 non-IBD controls. 
Results: The gene expression frequency of the TCR repertoire showed a clear separation between in the inflamed mucosa of patients with CD and healthy mucosa of non-IBD controls in the hierarchical clustering heatmap. The richness of TCR repertoires, measured by Chao1 index, were not significantly different among the groups, whereas diversity, measured by D50 diversity index, was decreased in the inflamed mucosa of CD patients. Rare/small TCR clonotypes occupied a large proportion of TCR repertoires in the healthy mucosa of controls, whereas expanded clonotypes were common in inflamed mucosa of patients with CD. The segment usage of TRAV2, TRAV22, TRAV40, TRJ14, TRAJ51, TRBV1, TRBV21.1, and TRBJ1.5 was significantly decreased in CD patients. KEGG enrichment analysis identified the enrichment of several KEGG terms, including inflammatory bowel disease (p = 0.0012), Th1 and Th2 cell differentiation (p = 0.0011), and intestinal immune network for IgA production (p = 0.0468). 
Conclusions: The diversity of TCR repertoire is reduced in inflamed mucosa of CD patients, which may contribute to intestinal inflammation.