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

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 regula...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Lisanne Lutter, Britt Roosenboom, Eelco C. Brand, José J. ter Linde, Bas Oldenburg, Ellen G. van Lochem, Carmen S. Horjus Talabur Horje, Femke van Wijk
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	CD8+ Tissue-Resident T Cell Gut Compartmentalization Transcriptome Anti-T Cell Trafficking Agents Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/a4509fd606384f5597875baba536cee4
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a4509fd606384f5597875baba536cee4
record_format	dspace
spelling	oai:doaj.org-article:a4509fd606384f5597875baba536cee42021-11-12T04:38:31ZHomeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary2352-345X10.1016/j.jcmgh.2021.06.022https://doaj.org/article/a4509fd606384f5597875baba536cee42021-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2352345X21001375https://doaj.org/toc/2352-345XBackground & 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.Lisanne LutterBritt RoosenboomEelco C. BrandJosé J. ter LindeBas OldenburgEllen G. van LochemCarmen S. Horjus Talabur HorjeFemke van WijkElsevierarticleCD8+ Tissue-Resident T CellGut CompartmentalizationTranscriptomeAnti-T Cell Trafficking AgentsDiseases of the digestive system. GastroenterologyRC799-869ENCellular and Molecular Gastroenterology and Hepatology, Vol 12, Iss 5, Pp 1567-1581 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	CD8+ Tissue-Resident T Cell Gut Compartmentalization Transcriptome Anti-T Cell Trafficking Agents Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	CD8+ Tissue-Resident T Cell Gut Compartmentalization Transcriptome Anti-T Cell Trafficking Agents Diseases of the digestive system. Gastroenterology RC799-869 Lisanne Lutter Britt Roosenboom Eelco C. Brand José J. ter Linde Bas Oldenburg Ellen G. van Lochem Carmen S. Horjus Talabur Horje Femke van Wijk Homeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary
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.
format	article
author	Lisanne Lutter Britt Roosenboom Eelco C. Brand José J. ter Linde Bas Oldenburg Ellen G. van Lochem Carmen S. Horjus Talabur Horje Femke van Wijk
author_facet	Lisanne Lutter Britt Roosenboom Eelco C. Brand José J. ter Linde Bas Oldenburg Ellen G. van Lochem Carmen S. Horjus Talabur Horje Femke van Wijk
author_sort	Lisanne Lutter
title	Homeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary
title_short	Homeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary
title_full	Homeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary
title_fullStr	Homeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary
title_full_unstemmed	Homeostatic Function and Inflammatory Activation of Ileal CD8+ Tissue-Resident T Cells Is Dependent on Mucosal LocationSummary
title_sort	homeostatic function and inflammatory activation of ileal cd8+ tissue-resident t cells is dependent on mucosal locationsummary
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/a4509fd606384f5597875baba536cee4
work_keys_str_mv	AT lisannelutter homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT brittroosenboom homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT eelcocbrand homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT josejterlinde homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT basoldenburg homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT ellengvanlochem homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT carmenshorjustalaburhorje homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary AT femkevanwijk homeostaticfunctionandinflammatoryactivationofilealcd8tissueresidenttcellsisdependentonmucosallocationsummary
_version_	1718431248254238720

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

Ejemplares similares