Work

Pro-inflammatory NK-like T cells are expanded in the blood and inflamed intestine in Crohn’s disease

Year: 2024

Type: article

Abstract: Altered intestinal immune homeostasis leads to chronic inflammation in Crohn's disease (CD). To address disease- and tissue-specific alterations, we performed a T cell-centric mass cytometry analysis of peripheral and intestinal lymphocytes from patients with CD and healthy donors' PBMCs. Chronic intestinal inflammation enforced activation, exhaustion, and terminal differentiation of CD4 + and CD8 + T cells and a relative enrichment of CD4 + regulatory T (Treg) cells. Moreover, enigmatic rare Treg subsets appeared upon inflammation, e.g. CD4 + FOXP3 + HLA-DR + TIGIT – and CD4 + FOXP3 + CD56 + , expressing pro-inflammatory IFN-γ upon in vitro stimulation. Some conventional T (Tcon) cells acquired NK-like features. In CD patients' blood, not well studied CD16 + CCR6 + CD127 + T cells appeared, being CD4 + or CD8 + , a phenotype inducible on healthy T cells by CD blood plasma. Upon CD16-mediated antibody binding, they could attain effector function. These findings suggest an uncommon pro-inflammatory innate-like differentiation of Treg and Tcon cells with acquisition of non-specific cytotoxicity. Most likely, this is both cause and consequence of intestinal inflammation during CD.

Source: Mucosal Immunology

DOI: 10.1016/j.mucimm.2024.11.001