| Autor: |
Kornberg, Adam, Botella, Theo, Moon, Christine S., Rao, Samhita, Gelbs, Jared, Cheng, Liang, Miller, Jonathan, Bacarella, Alyssa M., García-Vilas, Javier A., Vargas, Justin, Yu, Xuechen, Krupska, Izabela, Bush, Erin, Garcia-Carrasquillo, Reuben, Lebwohl, Benjamin, Krishnareddy, Suneeta, Lewis, Suzanne, Green, Peter H. R., Bhagat, Govind, Yan, Kelley S. |
| Zdroj: |
Science Immunology; 2023, Vol. 8 Issue 85, p1-15, 15p |
| Abstrakt: |
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+ αβ and γδ T-IELs. Natural CD8+ αβ 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 αβ 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. Editor's Summary: Celiac disease (CD) is an autoimmune disease for which the triggering antigen, ingested gluten, is well defined, thus facilitating investigation of immunological changes that lead to CD pathology. Kornberg et al. carried out multiplexed-single cell analysis of intestinal and peripheral blood T cells from patients with CD in different disease states as well as healthy controls. They identified distinct immune cell signatures, including elevated CD4+ follicular T-helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+ αβ and γδ intraepithelial T cells (T-IELs), in patients with untreated CD. The CD-associated TCR repertoire observed in natural killer receptor (NKR)-expressing natural CD8+ αβ and γδ T-IELs showed evidence of antigen-mediated selection. They also observed that in response to gluten ingestion, an NKR-expressing memory T-IEL subset gives rise to cytotoxic cells that appear to mediate CD-associated intestinal damage. —Christiana N. Fogg [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
