Keratinocytes determine Th1 immunity during early experimental leishmaniasis.

Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment...

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Autores principales:	Jan M Ehrchen, Kirsten Roebrock, Dirk Foell, Nadine Nippe, Esther von Stebut, Johannes M Weiss, Niels-Arne Münck, Dorothee Viemann, Georg Varga, Carsten Müller-Tidow, Hans-Joachim Schuberth, Johannes Roth, Cord Sunderkötter
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/6493a6742fe44136a6161639025b50cd
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spelling	oai:doaj.org-article:6493a6742fe44136a6161639025b50cd2021-12-02T20:00:43ZKeratinocytes determine Th1 immunity during early experimental leishmaniasis.1553-73661553-737410.1371/journal.ppat.1000871https://doaj.org/article/6493a6742fe44136a6161639025b50cd2010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20442861/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment of the early affected tissue delivers the initial triggers for Th-cell differentiation. To analyze this we studied differential gene expression in infected skin of resistant and susceptible mice 16h after parasite inoculation. Employing microarray technology, bioinformatics, laser-microdissection and in-situ-hybridization we found that the epidermis was the major source of immunomodulatory mediators. This epidermal gene induction was significantly stronger in resistant mice especially for several genes known to promote Th1 differentiation (IL-12, IL-1beta, osteopontin, IL-4) and for IL-6. Expression of these cytokines was temporally restricted to the crucial time of Th1/2 differentiation. Moreover, we revealed a stronger epidermal up-regulation of IL-6 in the epidermis of resistant mice. Accordingly, early local neutralization of IL-4 in resistant mice resulted in a Th2 switch and mice with a selective IL-6 deficiency in non-hematopoietic cells showed a Th2 switch and dramatic deterioration of disease. Thus, our data indicate for the first time that epidermal cytokine expression is a decisive factor in the generation of protective Th1 immunity and contributes to the outcome of infection with this important human pathogen.Jan M EhrchenKirsten RoebrockDirk FoellNadine NippeEsther von StebutJohannes M WeissNiels-Arne MünckDorothee ViemannGeorg VargaCarsten Müller-TidowHans-Joachim SchuberthJohannes RothCord SunderkötterPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 6, Iss 4, p e1000871 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jan M Ehrchen Kirsten Roebrock Dirk Foell Nadine Nippe Esther von Stebut Johannes M Weiss Niels-Arne Münck Dorothee Viemann Georg Varga Carsten Müller-Tidow Hans-Joachim Schuberth Johannes Roth Cord Sunderkötter Keratinocytes determine Th1 immunity during early experimental leishmaniasis.
description	Experimental leishmaniasis is an excellent model system for analyzing Th1/Th2 differentiation. Resistance to Leishmania (L.) major depends on the development of a L. major specific Th1 response, while Th2 differentiation results in susceptibility. There is growing evidence that the microenvironment of the early affected tissue delivers the initial triggers for Th-cell differentiation. To analyze this we studied differential gene expression in infected skin of resistant and susceptible mice 16h after parasite inoculation. Employing microarray technology, bioinformatics, laser-microdissection and in-situ-hybridization we found that the epidermis was the major source of immunomodulatory mediators. This epidermal gene induction was significantly stronger in resistant mice especially for several genes known to promote Th1 differentiation (IL-12, IL-1beta, osteopontin, IL-4) and for IL-6. Expression of these cytokines was temporally restricted to the crucial time of Th1/2 differentiation. Moreover, we revealed a stronger epidermal up-regulation of IL-6 in the epidermis of resistant mice. Accordingly, early local neutralization of IL-4 in resistant mice resulted in a Th2 switch and mice with a selective IL-6 deficiency in non-hematopoietic cells showed a Th2 switch and dramatic deterioration of disease. Thus, our data indicate for the first time that epidermal cytokine expression is a decisive factor in the generation of protective Th1 immunity and contributes to the outcome of infection with this important human pathogen.
format	article
author	Jan M Ehrchen Kirsten Roebrock Dirk Foell Nadine Nippe Esther von Stebut Johannes M Weiss Niels-Arne Münck Dorothee Viemann Georg Varga Carsten Müller-Tidow Hans-Joachim Schuberth Johannes Roth Cord Sunderkötter
author_facet	Jan M Ehrchen Kirsten Roebrock Dirk Foell Nadine Nippe Esther von Stebut Johannes M Weiss Niels-Arne Münck Dorothee Viemann Georg Varga Carsten Müller-Tidow Hans-Joachim Schuberth Johannes Roth Cord Sunderkötter
author_sort	Jan M Ehrchen
title	Keratinocytes determine Th1 immunity during early experimental leishmaniasis.
title_short	Keratinocytes determine Th1 immunity during early experimental leishmaniasis.
title_full	Keratinocytes determine Th1 immunity during early experimental leishmaniasis.
title_fullStr	Keratinocytes determine Th1 immunity during early experimental leishmaniasis.
title_full_unstemmed	Keratinocytes determine Th1 immunity during early experimental leishmaniasis.
title_sort	keratinocytes determine th1 immunity during early experimental leishmaniasis.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/6493a6742fe44136a6161639025b50cd
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_version_	1718375663836069888

Keratinocytes determine Th1 immunity during early experimental leishmaniasis.

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