Gluten induces rapid reprogramming of natural memory αß and γδ intraepithelial T cells to induce cytotoxicity in celiac disease.
Sci Immunol
; 8(85): eadf4312, 2023 07 21.
Article
em En
| MEDLINE
| ID: mdl-37450575
ABSTRACT
Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+ T cell activation culminates in intraepithelial T cell (T-IEL)-mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4+ follicular T helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+ αß and γδ T-IELs. Natural CD8+ αß and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αß and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4+ T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+ T cells after gluten ingestion.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença Celíaca
/
Linfócitos Intraepiteliais
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article