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Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location

BACKGROUND & AIMS: Tissue-resident memory T (Trm) cells, both of the CD4 and CD8 lineage, have been implicated in disease flares in inflammatory bowel disease. However, data are conflicting regarding the profile of human CD8(+) Trm cells, with studies suggesting both proinflammatory and regulato...

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Autores principales: Lutter, Lisanne, Roosenboom, Britt, Brand, Eelco C., ter Linde, José J., Oldenburg, Bas, van Lochem, Ellen G., Horjus Talabur Horje, Carmen S., van Wijk, Femke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551698/
https://www.ncbi.nlm.nih.gov/pubmed/34224909
http://dx.doi.org/10.1016/j.jcmgh.2021.06.022
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author Lutter, Lisanne
Roosenboom, Britt
Brand, Eelco C.
ter Linde, José J.
Oldenburg, Bas
van Lochem, Ellen G.
Horjus Talabur Horje, Carmen S.
van Wijk, Femke
author_facet Lutter, Lisanne
Roosenboom, Britt
Brand, Eelco C.
ter Linde, José J.
Oldenburg, Bas
van Lochem, Ellen G.
Horjus Talabur Horje, Carmen S.
van Wijk, Femke
author_sort Lutter, Lisanne
collection PubMed
description BACKGROUND & AIMS: Tissue-resident memory T (Trm) cells, both of the CD4 and CD8 lineage, have been implicated in disease flares in inflammatory bowel disease. However, data are conflicting regarding the profile of human CD8(+) Trm cells, with studies suggesting both proinflammatory and regulatory functions. It is crucial to understand the functional profile of these cells in the context of (new) therapeutic strategies targeting (trafficking of) gut Trm cells. METHODS: Here, we performed imaging mass cytometry, flow cytometry, and RNA-sequencing to compare lamina propria and intraepithelial CD103(+/–)CD69(+)CD8(+) Trm cells in healthy control subjects and patients with active ileal Crohn’s disease. RESULTS: Our data revealed that lamina propria CD103(+)CD69(+)CD8(+) T cells have a classical Trm cell profile with active pathways for regulating cell survival/death and cytokine signaling, whereas intraepithelial CD103(+)CD69(+)CD8(+) T cells display tightly regulated innate-like cytotoxic profile. Furthermore, within lamina propria CD8(+)CD103(–) Trm cells, an Itgb2(+)GzmK(+)KLRG1(+) population distinct from CD103(+) CD8(+) Trm cells is found. During chronic inflammation, especially intraepithelial CD103(+)CD69(+)CD8(+) T cells displayed an innate proinflammatory profile with concurrent loss of homeostatic functions. CONCLUSIONS: Altogether, these compartmental and inflammation-induced differences indicate that therapeutic strategies could have a different impact on the same immune cells depending on the local compartment and presence of an inflammatory milieu, and should be taken into account when investigating short- and long-term effects of new gut T cell–targeting drugs.
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spelling pubmed-85516982021-11-04 Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location Lutter, Lisanne Roosenboom, Britt Brand, Eelco C. ter Linde, José J. Oldenburg, Bas van Lochem, Ellen G. Horjus Talabur Horje, Carmen S. van Wijk, Femke Cell Mol Gastroenterol Hepatol Original Research BACKGROUND & AIMS: Tissue-resident memory T (Trm) cells, both of the CD4 and CD8 lineage, have been implicated in disease flares in inflammatory bowel disease. However, data are conflicting regarding the profile of human CD8(+) Trm cells, with studies suggesting both proinflammatory and regulatory functions. It is crucial to understand the functional profile of these cells in the context of (new) therapeutic strategies targeting (trafficking of) gut Trm cells. METHODS: Here, we performed imaging mass cytometry, flow cytometry, and RNA-sequencing to compare lamina propria and intraepithelial CD103(+/–)CD69(+)CD8(+) Trm cells in healthy control subjects and patients with active ileal Crohn’s disease. RESULTS: Our data revealed that lamina propria CD103(+)CD69(+)CD8(+) T cells have a classical Trm cell profile with active pathways for regulating cell survival/death and cytokine signaling, whereas intraepithelial CD103(+)CD69(+)CD8(+) T cells display tightly regulated innate-like cytotoxic profile. Furthermore, within lamina propria CD8(+)CD103(–) Trm cells, an Itgb2(+)GzmK(+)KLRG1(+) population distinct from CD103(+) CD8(+) Trm cells is found. During chronic inflammation, especially intraepithelial CD103(+)CD69(+)CD8(+) T cells displayed an innate proinflammatory profile with concurrent loss of homeostatic functions. CONCLUSIONS: Altogether, these compartmental and inflammation-induced differences indicate that therapeutic strategies could have a different impact on the same immune cells depending on the local compartment and presence of an inflammatory milieu, and should be taken into account when investigating short- and long-term effects of new gut T cell–targeting drugs. Elsevier 2021-07-02 /pmc/articles/PMC8551698/ /pubmed/34224909 http://dx.doi.org/10.1016/j.jcmgh.2021.06.022 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research
Lutter, Lisanne
Roosenboom, Britt
Brand, Eelco C.
ter Linde, José J.
Oldenburg, Bas
van Lochem, Ellen G.
Horjus Talabur Horje, Carmen S.
van Wijk, Femke
Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location
title Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location
title_full Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location
title_fullStr Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location
title_full_unstemmed Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location
title_short Homeostatic Function and Inflammatory Activation of Ileal CD8(+) Tissue-Resident T Cells Is Dependent on Mucosal Location
title_sort homeostatic function and inflammatory activation of ileal cd8(+) tissue-resident t cells is dependent on mucosal location
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8551698/
https://www.ncbi.nlm.nih.gov/pubmed/34224909
http://dx.doi.org/10.1016/j.jcmgh.2021.06.022
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