Active eosinophils regulate host defence and immune responses in colitis

Autores
Gurtner, Alessandra; Borrelli, Costanza; Gonzalez Perez, Ignacio; Bach, Karsten; Acar, Ilhan E.; Núñez, Nicolás; Crepaz, Daniel; Handler, Kristina; Vu, Vivian P.; Lafzi, Atefeh; Stirm, Kristin; Raju, Deeksha; Gschwend, Julia; Basler, Konrad; Schneider, Christoph; Slack, Emma; Valenta, Tomas; Becher, Burkhard; Krebs, Philippe; Moor, Andreas E.; Arnold, Isabelle C.
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils—elusive granulocytes that are implicated in a plethora of human pathologies1–5—are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
Fil: Gurtner, Alessandra. Universitat Zurich; Suiza
Fil: Borrelli, Costanza. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Gonzalez Perez, Ignacio. Universitat Zurich; Suiza
Fil: Bach, Karsten. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Acar, Ilhan E.. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Crepaz, Daniel. Universitat Zurich; Suiza
Fil: Handler, Kristina. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Vu, Vivian P.. University of Bern; Suiza
Fil: Lafzi, Atefeh. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Stirm, Kristin. Universitat Zurich; Suiza
Fil: Raju, Deeksha. Universitat Zurich; Suiza
Fil: Gschwend, Julia. Universitat Zurich; Suiza
Fil: Basler, Konrad. Universitat Zurich; Suiza
Fil: Schneider, Christoph. Universitat Zurich; Suiza
Fil: Slack, Emma. Botnar Research Centre For Child Health; Suiza. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Valenta, Tomas. Institute of molecular genetics of the Academy Of Sciences Of The Czech Republic; República Checa. Universitat Zurich; Suiza
Fil: Becher, Burkhard. Universitat Zurich; Suiza
Fil: Krebs, Philippe. University of Bern; Suiza
Fil: Moor, Andreas E.. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Arnold, Isabelle C.. Universitat Zurich; Suiza
Materia
Cancer
Eosinófilos
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/212112
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/212112
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Active eosinophils regulate host defence and immune responses in colitisGurtner, AlessandraBorrelli, CostanzaGonzalez Perez, IgnacioBach, KarstenAcar, Ilhan E.Núñez, NicolásCrepaz, DanielHandler, KristinaVu, Vivian P.Lafzi, AtefehStirm, KristinRaju, DeekshaGschwend, JuliaBasler, KonradSchneider, ChristophSlack, EmmaValenta, TomasBecher, BurkhardKrebs, PhilippeMoor, Andreas E.Arnold, Isabelle C.CancerEosinófiloshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils—elusive granulocytes that are implicated in a plethora of human pathologies1–5—are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.Fil: Gurtner, Alessandra. Universitat Zurich; SuizaFil: Borrelli, Costanza. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Gonzalez Perez, Ignacio. Universitat Zurich; SuizaFil: Bach, Karsten. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Acar, Ilhan E.. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Crepaz, Daniel. Universitat Zurich; SuizaFil: Handler, Kristina. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Vu, Vivian P.. University of Bern; SuizaFil: Lafzi, Atefeh. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Stirm, Kristin. Universitat Zurich; SuizaFil: Raju, Deeksha. Universitat Zurich; SuizaFil: Gschwend, Julia. Universitat Zurich; SuizaFil: Basler, Konrad. Universitat Zurich; SuizaFil: Schneider, Christoph. Universitat Zurich; SuizaFil: Slack, Emma. Botnar Research Centre For Child Health; Suiza. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Valenta, Tomas. Institute of molecular genetics of the Academy Of Sciences Of The Czech Republic; República Checa. Universitat Zurich; SuizaFil: Becher, Burkhard. Universitat Zurich; SuizaFil: Krebs, Philippe. University of Bern; SuizaFil: Moor, Andreas E.. ETH Zürich. Department of Biosystems Science and Engineering; SuizaFil: Arnold, Isabelle C.. Universitat Zurich; SuizaNature Publishing Group2023-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/212112Gurtner, Alessandra; Borrelli, Costanza; Gonzalez Perez, Ignacio; Bach, Karsten; Acar, Ilhan E.; et al.; Active eosinophils regulate host defence and immune responses in colitis; Nature Publishing Group; Nature; 615; 7950; 3-2023; 151-1570028-08361476-4687CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41586-022-05628-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T15:07:16Zoai:ri.conicet.gov.ar:11336/212112instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 15:07:16.367CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Active eosinophils regulate host defence and immune responses in colitis
title Active eosinophils regulate host defence and immune responses in colitis
spellingShingle Active eosinophils regulate host defence and immune responses in colitis
Gurtner, Alessandra
Cancer
Eosinófilos
title_short Active eosinophils regulate host defence and immune responses in colitis
title_full Active eosinophils regulate host defence and immune responses in colitis
title_fullStr Active eosinophils regulate host defence and immune responses in colitis
title_full_unstemmed Active eosinophils regulate host defence and immune responses in colitis
title_sort Active eosinophils regulate host defence and immune responses in colitis
dc.creator.none.fl_str_mv Gurtner, Alessandra
Borrelli, Costanza
Gonzalez Perez, Ignacio
Bach, Karsten
Acar, Ilhan E.
Núñez, Nicolás
Crepaz, Daniel
Handler, Kristina
Vu, Vivian P.
Lafzi, Atefeh
Stirm, Kristin
Raju, Deeksha
Gschwend, Julia
Basler, Konrad
Schneider, Christoph
Slack, Emma
Valenta, Tomas
Becher, Burkhard
Krebs, Philippe
Moor, Andreas E.
Arnold, Isabelle C.
author Gurtner, Alessandra
author_facet Gurtner, Alessandra
Borrelli, Costanza
Gonzalez Perez, Ignacio
Bach, Karsten
Acar, Ilhan E.
Núñez, Nicolás
Crepaz, Daniel
Handler, Kristina
Vu, Vivian P.
Lafzi, Atefeh
Stirm, Kristin
Raju, Deeksha
Gschwend, Julia
Basler, Konrad
Schneider, Christoph
Slack, Emma
Valenta, Tomas
Becher, Burkhard
Krebs, Philippe
Moor, Andreas E.
Arnold, Isabelle C.
author_role author
author2 Borrelli, Costanza
Gonzalez Perez, Ignacio
Bach, Karsten
Acar, Ilhan E.
Núñez, Nicolás
Crepaz, Daniel
Handler, Kristina
Vu, Vivian P.
Lafzi, Atefeh
Stirm, Kristin
Raju, Deeksha
Gschwend, Julia
Basler, Konrad
Schneider, Christoph
Slack, Emma
Valenta, Tomas
Becher, Burkhard
Krebs, Philippe
Moor, Andreas E.
Arnold, Isabelle C.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cancer
Eosinófilos
topic Cancer
Eosinófilos
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils—elusive granulocytes that are implicated in a plethora of human pathologies1–5—are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
Fil: Gurtner, Alessandra. Universitat Zurich; Suiza
Fil: Borrelli, Costanza. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Gonzalez Perez, Ignacio. Universitat Zurich; Suiza
Fil: Bach, Karsten. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Acar, Ilhan E.. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Núñez, Nicolás. Universitat Zurich; Suiza. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
Fil: Crepaz, Daniel. Universitat Zurich; Suiza
Fil: Handler, Kristina. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Vu, Vivian P.. University of Bern; Suiza
Fil: Lafzi, Atefeh. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Stirm, Kristin. Universitat Zurich; Suiza
Fil: Raju, Deeksha. Universitat Zurich; Suiza
Fil: Gschwend, Julia. Universitat Zurich; Suiza
Fil: Basler, Konrad. Universitat Zurich; Suiza
Fil: Schneider, Christoph. Universitat Zurich; Suiza
Fil: Slack, Emma. Botnar Research Centre For Child Health; Suiza. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Valenta, Tomas. Institute of molecular genetics of the Academy Of Sciences Of The Czech Republic; República Checa. Universitat Zurich; Suiza
Fil: Becher, Burkhard. Universitat Zurich; Suiza
Fil: Krebs, Philippe. University of Bern; Suiza
Fil: Moor, Andreas E.. ETH Zürich. Department of Biosystems Science and Engineering; Suiza
Fil: Arnold, Isabelle C.. Universitat Zurich; Suiza
description In the past decade, single-cell transcriptomics has helped to uncover new cell types and states and led to the construction of a cellular compendium of health and disease. Despite this progress, some difficult-to-sequence cells remain absent from tissue atlases. Eosinophils—elusive granulocytes that are implicated in a plethora of human pathologies1–5—are among these uncharted cell types. The heterogeneity of eosinophils and the gene programs that underpin their pleiotropic functions remain poorly understood. Here we provide a comprehensive single-cell transcriptomic profiling of mouse eosinophils. We identify an active and a basal population of intestinal eosinophils, which differ in their transcriptome, surface proteome and spatial localization. By means of a genome-wide CRISPR inhibition screen and functional assays, we reveal a mechanism by which interleukin-33 (IL-33) and interferon-γ (IFNγ) induce the accumulation of active eosinophils in the inflamed colon. Active eosinophils are endowed with bactericidal and T cell regulatory activity, and express the co-stimulatory molecules CD80 and PD-L1. Notably, active eosinophils are enriched in the lamina propria of a small cohort of patients with inflammatory bowel disease, and are closely associated with CD4+ T cells. Our findings provide insights into the biology of eosinophils and highlight the crucial contribution of this cell type to intestinal homeostasis, immune regulation and host defence. Furthermore, we lay a framework for the characterization of eosinophils in human gastrointestinal diseases.
publishDate 2023
dc.date.none.fl_str_mv 2023-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/212112
Gurtner, Alessandra; Borrelli, Costanza; Gonzalez Perez, Ignacio; Bach, Karsten; Acar, Ilhan E.; et al.; Active eosinophils regulate host defence and immune responses in colitis; Nature Publishing Group; Nature; 615; 7950; 3-2023; 151-157
0028-0836
1476-4687
CONICET Digital
CONICET
url http://hdl.handle.net/11336/212112
identifier_str_mv Gurtner, Alessandra; Borrelli, Costanza; Gonzalez Perez, Ignacio; Bach, Karsten; Acar, Ilhan E.; et al.; Active eosinophils regulate host defence and immune responses in colitis; Nature Publishing Group; Nature; 615; 7950; 3-2023; 151-157
0028-0836
1476-4687
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/s41586-022-05628-7
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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