IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis

Background/Aims: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopath...

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Main Authors: Virginia Seiffart, Julia Zoeller, Robert Klopfleisch, Munisch Wadwa, Wiebke Hansen, Jan Buer, Christian Riedel, Astrid M. Westendorf
Format: Article
Language:English
Published: Cell Physiol Biochem Press GmbH & Co KG 2015-07-01
Series:Cellular Physiology and Biochemistry
Subjects:
Online Access:http://www.karger.com/Article/FullText/430295
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author Virginia Seiffart
Julia Zoeller
Robert Klopfleisch
Munisch Wadwa
Wiebke Hansen
Jan Buer
Christian Riedel
Astrid M. Westendorf
author_facet Virginia Seiffart
Julia Zoeller
Robert Klopfleisch
Munisch Wadwa
Wiebke Hansen
Jan Buer
Christian Riedel
Astrid M. Westendorf
author_sort Virginia Seiffart
collection DOAJ
description Background/Aims: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation. Methods: Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C.) rodentium and analyzed for the specific immune response and pathogloy in the colon. Results: We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNγ and IL17 response in the colon. Conclusion: Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation.
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spelling doaj.art-c7ecd8a34beb455e91ffaa9a27acfa6a2022-12-22T01:09:17ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-07-013641259127310.1159/000430295430295IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced ColitisVirginia SeiffartJulia ZoellerRobert KlopfleischMunisch WadwaWiebke HansenJan BuerChristian RiedelAstrid M. WestendorfBackground/Aims: IL10 is a key inhibitor of effector T cell activation and a mediator of intestinal homeostasis. In addition, IL10 has emerged as a key immunoregulator during infection with various pathogens, ameliorating the excessive T-cell responses that are responsible for much of the immunopathology associated with the infection. Because IL10 plays an important role in both intestinal homeostasis and infection, we studied the function of IL10 in infection-associated intestinal inflammation. Methods: Wildtype mice and mice deficient in CD4+ T cell-derived or regulatory T cells-derived IL10 were infected with the enteric pathogen Citrobacter (C.) rodentium and analyzed for the specific immune response and pathogloy in the colon. Results: We found that IL10 expression is upregulated in colonic tissue after infection with C. rodentium, especially in CD4+ T cells, macrophages and dendritic cells. Whereas the deletion of IL10 in regulatory T cells had no effect on C. rodentium induced colitis, infection of mice deficient in CD4+ T cell-derived IL10 exhibited faster clearance of the bacterial burden but worse colitis, crypt hyperplasia, and pathology than did WT mice. In addition, the depletion of CD4+ T cell-derived IL10 in infected animals was accompanied by an accelerated IFNγ and IL17 response in the colon. Conclusion: Thus, we conclude that CD4+ T cell-derived IL10 is strongly involved in the control of C. rodentium-induced colitis. Interference with this network could have implications for the treatment of infection-associated intestinal inflammation.http://www.karger.com/Article/FullText/430295Citrobacter rodentiumInterleukin 10T helper cell 17Colitis
spellingShingle Virginia Seiffart
Julia Zoeller
Robert Klopfleisch
Munisch Wadwa
Wiebke Hansen
Jan Buer
Christian Riedel
Astrid M. Westendorf
IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
Cellular Physiology and Biochemistry
Citrobacter rodentium
Interleukin 10
T helper cell 17
Colitis
title IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
title_full IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
title_fullStr IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
title_full_unstemmed IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
title_short IL10-Deficiency in CD4+ T Cells Exacerbates the IFNγ and IL17 Response During Bacteria Induced Colitis
title_sort il10 deficiency in cd4 t cells exacerbates the ifn 947 and il17 response during bacteria induced colitis
topic Citrobacter rodentium
Interleukin 10
T helper cell 17
Colitis
url http://www.karger.com/Article/FullText/430295
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