2.50
HDL Handle:
http://hdl.handle.net/10033/251560
Title:
IL-4 Attenuates Pulmonary Epithelial Cell-Mediated Suppression of T Cell Priming.
Authors:
Albrecht, Melanie; Arnhold, Markus; Lingner, Sandra; Mahapatra, Subhashree; Bruder, Dunja; Hansen, Gesine; Dittrich, Anna-Maria
Abstract:
We have previously shown that Th2-polarized airway inflammation facilitates sensitization towards new, protein antigens. In this context, we could demonstrate that IL-4 needs to act on cells of the hematopoetic and the structural compartment in order to facilitate sensitization towards new antigens. We thus aimed to elucidate possible mechanisms of action of IL-4 on structural cells choosing to analyze pulmonary epithelial cells as an important part of the lung's structural system. We used a co-culture system of DC- or APC-dependent in vitro priming of T cells, co-cultivated on a layer of cells of a murine pulmonary epithelial cell line (LA-4) pretreated with or without IL-4. Effects on T cell priming were analyzed via CFSE-dilution and flow cytometric assessment of activation status. Pulmonary epithelial cells suppressed T cell proliferation in vitro but this effect was attenuated by pre-treatment of the epithelial cells with IL-4. Transwell experiments suggest that epithelial-mediated suppression of T cell activation is mostly cell-contact dependent and leads to attenuation in an early naive T cell phenotype. Secretion of soluble factors like TARC, TSLP, GM-CSF and CCL20 by epithelial cells did not change after IL-4 treatment. However, analysis of co-stimulatory expression on pulmonary epithelial cells revealed that pre-treatment of epithelial cells with IL-4 changed expression GITR-L, suggesting a possible mechanism for the effects observed. Our studies provide new insight into the role of IL-4 during the early phases of pulmonary sensitization: The inhibitory activity of pulmonary epithelial cells in homeostasis is reversed in the presence of IL-4, which is secreted in the context of Th2-dominated allergic airway inflammation. This mechanism might serve to explain facilitated sensitization in the clinical context of polysensitization where due to a pre-existing sensitization increased levels of IL-4 in the airways might facilitate T cell priming towards new antigens.
Affiliation:
Pediatric Pneumology, Allergology and Neonatology, Medical School Hannover, Hannover, Germany.
Citation:
IL-4 Attenuates Pulmonary Epithelial Cell-Mediated Suppression of T Cell Priming. 2012, 7 (9):e45916 PLoS ONE
Journal:
PloS one
Issue Date:
2012
URI:
http://hdl.handle.net/10033/251560
DOI:
10.1371/journal.pone.0045916
PubMed ID:
23029313
Type:
Article
Language:
en
ISSN:
1932-6203
Appears in Collections:
publications of the AG Immunregulation (IREG)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorAlbrecht, Melanieen_GB
dc.contributor.authorArnhold, Markusen_GB
dc.contributor.authorLingner, Sandraen_GB
dc.contributor.authorMahapatra, Subhashreeen_GB
dc.contributor.authorBruder, Dunjaen_GB
dc.contributor.authorHansen, Gesineen_GB
dc.contributor.authorDittrich, Anna-Mariaen_GB
dc.date.accessioned2012-11-09T13:40:45Z-
dc.date.available2012-11-09T13:40:45Z-
dc.date.issued2012-
dc.identifier.citationIL-4 Attenuates Pulmonary Epithelial Cell-Mediated Suppression of T Cell Priming. 2012, 7 (9):e45916 PLoS ONEen_GB
dc.identifier.issn1932-6203-
dc.identifier.pmid23029313-
dc.identifier.doi10.1371/journal.pone.0045916-
dc.identifier.urihttp://hdl.handle.net/10033/251560-
dc.description.abstractWe have previously shown that Th2-polarized airway inflammation facilitates sensitization towards new, protein antigens. In this context, we could demonstrate that IL-4 needs to act on cells of the hematopoetic and the structural compartment in order to facilitate sensitization towards new antigens. We thus aimed to elucidate possible mechanisms of action of IL-4 on structural cells choosing to analyze pulmonary epithelial cells as an important part of the lung's structural system. We used a co-culture system of DC- or APC-dependent in vitro priming of T cells, co-cultivated on a layer of cells of a murine pulmonary epithelial cell line (LA-4) pretreated with or without IL-4. Effects on T cell priming were analyzed via CFSE-dilution and flow cytometric assessment of activation status. Pulmonary epithelial cells suppressed T cell proliferation in vitro but this effect was attenuated by pre-treatment of the epithelial cells with IL-4. Transwell experiments suggest that epithelial-mediated suppression of T cell activation is mostly cell-contact dependent and leads to attenuation in an early naive T cell phenotype. Secretion of soluble factors like TARC, TSLP, GM-CSF and CCL20 by epithelial cells did not change after IL-4 treatment. However, analysis of co-stimulatory expression on pulmonary epithelial cells revealed that pre-treatment of epithelial cells with IL-4 changed expression GITR-L, suggesting a possible mechanism for the effects observed. Our studies provide new insight into the role of IL-4 during the early phases of pulmonary sensitization: The inhibitory activity of pulmonary epithelial cells in homeostasis is reversed in the presence of IL-4, which is secreted in the context of Th2-dominated allergic airway inflammation. This mechanism might serve to explain facilitated sensitization in the clinical context of polysensitization where due to a pre-existing sensitization increased levels of IL-4 in the airways might facilitate T cell priming towards new antigens.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PloS oneen_GB
dc.titleIL-4 Attenuates Pulmonary Epithelial Cell-Mediated Suppression of T Cell Priming.en
dc.typeArticleen
dc.contributor.departmentPediatric Pneumology, Allergology and Neonatology, Medical School Hannover, Hannover, Germany.en_GB
dc.identifier.journalPloS oneen_GB

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