Pro-inflammatory NK-like T cells are expanded in the blood and inflamed intestine in Crohn’s disease
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<sup>+</sup> and CD8<sup>+</sup> T cells and a relative enrichment of CD4<sup>+</sup> regulatory T (Treg) cells. Moreover, enigmatic rare Treg subsets appeared upon inflammation, e.g. CD4<sup>+</sup>FOXP3<sup>+</sup>HLA-DR<sup>+</sup>TIGIT<sup>-</sup> and CD4<sup>+</sup>FOXP3<sup>+</sup>CD56<sup>+</sup>, 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<sup>+</sup>CCR6<sup>+</sup>CD127<sup>+</sup> T cells appeared, being CD4<sup>+</sup> or CD8<sup>+</sup>, 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.
Authors
- Martina Prelog (ORCID: https://orcid.org/0000-0003-2034-2764)
- Axel Schulz (ORCID: https://orcid.org/0000-0002-5106-0148)
- Maike Büttner‐Herold (ORCID: https://orcid.org/0000-0002-9974-6683)
- Henrik E. Mei (ORCID: https://orcid.org/0000-0003-0697-7755)
- Addi J. Romero‐Olmedo (ORCID: https://orcid.org/0000-0001-7772-9746)
- Nicolas Schlegel (ORCID: https://orcid.org/0000-0001-5705-3945)
- Andreas Rosenwald (ORCID: https://orcid.org/0000-0001-7282-8374)
- Hyun‐Dong Chang (ORCID: https://orcid.org/0000-0002-7341-4533)
- Hartmut Hengel (ORCID: https://orcid.org/0000-0002-3482-816X)
- Katja Hoffmann (ORCID: https://orcid.org/0000-0003-3749-9047)
- Michael Lohoff (ORCID: https://orcid.org/0000-0002-5204-4289)
- Valeria Falcone (ORCID: https://orcid.org/0000-0003-1180-8737)
- Cristina M. Chiarolla
- Simone Reu‐Hofer
- Michael Meir (ORCID: https://orcid.org/0000-0002-4172-1176)
- Friederike Berberich‐Siebelt (ORCID: https://orcid.org/0000-0003-1673-4175)
- Yin Xiao (ORCID: https://orcid.org/0000-0001-9277-1707)
- Sebastian Ferrara
Institutions
- Philipps University of Marburg (DE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Würzburg (DE)
- German Rheumatism Research Centre (DE)
- Universitätsklinikum Würzburg (DE)
Publication Details
- Journal
- Mucosal Immunology
- Published
- 2024-11-07
- DOI
- https://doi.org/10.1016/j.mucimm.2024.11.001
- Citations
- 2
- Primary Topic
- Microscopic Colitis
- Type
- article
- Field-Weighted Citation Impact
- 0.77
Funders
- Wilhelm Sander-Stiftung
- Deutsche Forschungsgemeinschaft
- Else Kröner-Fresenius-Stiftung
- Fritz Thyssen Stiftung
- Deutsche Krebshilfe