@misc{10481/106559,
year = {2025},
month = {9},
url = {https://hdl.handle.net/10481/106559},
abstract = {Celiac disease (CD) is a chronic autoimmune disorder triggered by gluten in genetically
susceptible individuals. While gluten-free diet (GFD) remains the primary treatment, the
molecular mechanisms underlying immune reconstitution remain poorly understood in
pediatric populations. This study aimed to characterize T cell receptor (TCR) repertoire
remodeling in pediatric CD patients following short-term GFD. We conducted a longitudinal observational study analyzing peripheral blood circulating T cells from five pediatric
CD patients at two time points: pre-GFD (at diagnosis) and post-GFD (after 9–10 months
of strict dietary adherence). Single-cell TCR sequencing was performed to analyze clonotype diversity, gene usage patterns and TRAV-TRBV pairing combinations. Analysis of
9661 T cells revealed significant TCR repertoire remodeling post-GFD. Expanded clones,
predominantly cytotoxic CD8+ T cells, contracted post-GFD (p = 0.02), while increasing
clonotype diversity. Notably, specific αβ chain pairings underwent clear reorganization
in the complete T cell compartment. Pathogenic combinations were depleted post-GFD,
especially in CD4+ T cells, while beneficial pairings became enriched. GFD induced comprehensive TCR repertoire remodeling, revealing that changes occur at the level of specific
TCR pairings rather than individual gene usage. Our findings highlight the precision of
single-cell approaches in capturing functionally relevant immune changes for monitoring
treatment response in pediatric CD.},
organization = {Consejería de Salud
y Consumo-Junta de Andalucía (PI-0070-2024)},
organization = {Consejería de Universidad, Investigación e Innovación - ERDF Andalusia
Program 2021-2027 (grant C-CTS-301-
UGR23)},
organization = {Sociedad Española de Gastroenterología, Hepatología y Nutrición Pediátrica (SEGHNP) 2023 edition},
organization = {MICIU/AEI/10.13039/501100011033 - European Union Next GenerationEU/PRTR (Ramon y Cajal fellowship, RYC2021-034816-I)},
publisher = {MDPI},
keywords = {Celiac disease},
keywords = {TCR},
keywords = {T cells},
title = {Single-Cell TCR Sequencing Uncovers Remodeling of the Immune Repertoire After a Short-Term Gluten-Free Diet in Pediatric Celiac Disease},
doi = {10.3390/ijms26188927},
author = {Martín Masot, Rafael and Herrador-López, Marta and Navas-López, Víctor Manuel and Carmona López, Francisco David and González-Muñoz, Sara and López-Isac, Elena and Nestares Pleguezuelo, María Teresa and Bossini-Castillo, Lara},
}