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

• Published in: Mucosal immunology
• Main Authors: Chiarolla, Cristina M., Schulz, Axel R., Meir, Michael, Ferrara, Sebastian, Xiao, Yin, Reu-Hofer, Simone, Romero-Olmedo, Addi J., Falcone, Valeria, Hoffmann, Katja, Büttner-Herold, Maike, Prelog, Martina, Rosenwald, Andreas, Hengel, Hartmut, Lohoff, Michael, Chang, Hyun-Dong, Schlegel, Nicolas, Mei, Henrik E., Berberich-Siebelt, Friederike
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 07-11-2024
• Subjects: CD16+ T cells; CD56; Crohn’s Disease; CyTOF; TIGIT– eTreg; Crohn’s Disease; Inf; ILC; TCR; LP; CD16+ T cells; Treg; Tcon; TEMRA; TIGIT– eTreg; TPH; TRM; MFI; Not Inf; TFH; HD; CyTOF; CD56; ADCC; TEM; TCM
• ISSN: 1933-0219; 1935-3456; 1935-3456
• DOI: 10.1016/j.mucimm.2024.11.001

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•loss of tissue-protecting T cells.•activation, exhaustion and senescence for both CD4+ and CD8+ T cells.•acquired NK-like effector phenotypes of adaptive T cells.•circulating, plasma-inducible, cytotoxic, NK-like CD16+CCR6+ T cells.•partly pro-inflammatory Tregs in inflamed areas of CD patients’ intestine.
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.