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Lung Fibroblasts and Airway Epithelial Cells Activate Dendritic Cells and Shape Their Microenvironment In Vitro

Kadefors, Måns LU (2016) KIM820 20161
Department of Immunotechnology
Educational programmes, LTH
Abstract
Dendritic cells (DCs) are influenced by signals from their microenvironment, which may affect how they regulate immunity. Activation of T helper (Th) 2 cells by DCs in allergic reactions is well supported, yet the underlying mechanisms that regulate DCs to stimulate Th2 development are less clear. Airway epithelial cells (AECs) have been suggested as potent regulators of DCs and drivers of DC induced Th2 immunity through interactions with allergens such as house dust mite (HDM). Fibroblasts have also demonstrated immunoregulatory abilities; however, their influence on DC regulation, in particular with regard to allergy development, remain elusive. Recent unpublished data suggests an immunosuppressive role of fibroblast exhibited by reduced... (More)
Dendritic cells (DCs) are influenced by signals from their microenvironment, which may affect how they regulate immunity. Activation of T helper (Th) 2 cells by DCs in allergic reactions is well supported, yet the underlying mechanisms that regulate DCs to stimulate Th2 development are less clear. Airway epithelial cells (AECs) have been suggested as potent regulators of DCs and drivers of DC induced Th2 immunity through interactions with allergens such as house dust mite (HDM). Fibroblasts have also demonstrated immunoregulatory abilities; however, their influence on DC regulation, in particular with regard to allergy development, remain elusive. Recent unpublished data suggests an immunosuppressive role of fibroblast exhibited by reduced DC maturation in fibroblast co-cultures. To investigate the interplay between these cells, an in vitro system mimicking the airway microenvironment was developed with monocyte-derived dendritic cells (MoDCs), lung fibroblasts (HFL1) and bronchial epithelial cells (16HBE14o-). We have shown that the designed triple-culture system induces a pro-inflammatory and immunostimulatory milieu for DCs through increased TNF-α, IL-6 and PGE2 levels. In addition, levels of the Th2 promoting cytokines GM-CSF and IL-10 were also increased. These effects were, in part, amplified by stimulation with HDM allergen accompanied by a donor-dependent increase in DC maturation. Conversely, TNF-α and IL-12p70 levels were suppressed in MoDC and HFL1 co-cultures. To conclude, we present a promising system to study respiratory fibroblast and EC influence on DCs through evaluation of cytokine production and DC maturation in an in vitro triple-culture. (Less)
Popular Abstract (Swedish)
Förekomsten av luftvägsallergier som astma och hösnuva har ökat under de senaste årtiondena. Dessa sjukdomar kan leda till fysiska och psykosociala besvär; astma kan i värsta fall få fatala konsekvenser. Dendritceller är skickliga regulatorer av immunförsvaret och av allergiska reaktioner. I den här studien har vi i en cellkulturmodell undersökt hur dendritceller kan påverkas av deras närmiljö i luftvägarna och vad det kan ha för implikationer för allergiutveckling.
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author
Kadefors, Måns LU
supervisor
organization
alternative title
Lung Fibroblasts and Airway Epithelial Cells Activate Dendritic Cells and Shape Their Microenvironment In Vitro - Developing a Triple-Culture to Investigate Dendritic Cell Regulation in Allergic Reactions
course
KIM820 20161
year
type
H2 - Master's Degree (Two Years)
subject
keywords
Dendritic Cells, Fibroblasts, Epithelial Cells, Airways, Co-Culture, Allergy, Immunotechnology
language
English
id
8886965
date added to LUP
2016-07-08 10:12:50
date last changed
2016-07-08 10:12:50
@misc{8886965,
  abstract     = {Dendritic cells (DCs) are influenced by signals from their microenvironment, which may affect how they regulate immunity. Activation of T helper (Th) 2 cells by DCs in allergic reactions is well supported, yet the underlying mechanisms that regulate DCs to stimulate Th2 development are less clear. Airway epithelial cells (AECs) have been suggested as potent regulators of DCs and drivers of DC induced Th2 immunity through interactions with allergens such as house dust mite (HDM). Fibroblasts have also demonstrated immunoregulatory abilities; however, their influence on DC regulation, in particular with regard to allergy development, remain elusive. Recent unpublished data suggests an immunosuppressive role of fibroblast exhibited by reduced DC maturation in fibroblast co-cultures. To investigate the interplay between these cells, an in vitro system mimicking the airway microenvironment was developed with monocyte-derived dendritic cells (MoDCs), lung fibroblasts (HFL1) and bronchial epithelial cells (16HBE14o-). We have shown that the designed triple-culture system induces a pro-inflammatory and immunostimulatory milieu for DCs through increased TNF-α, IL-6 and PGE2 levels. In addition, levels of the Th2 promoting cytokines GM-CSF and IL-10 were also increased. These effects were, in part, amplified by stimulation with HDM allergen accompanied by a donor-dependent increase in DC maturation. Conversely, TNF-α and IL-12p70 levels were suppressed in MoDC and HFL1 co-cultures. To conclude, we present a promising system to study respiratory fibroblast and EC influence on DCs through evaluation of cytokine production and DC maturation in an in vitro triple-culture.},
  author       = {Kadefors, Måns},
  keyword      = {Dendritic Cells,Fibroblasts,Epithelial Cells,Airways,Co-Culture,Allergy,Immunotechnology},
  language     = {eng},
  note         = {Student Paper},
  title        = {Lung Fibroblasts and Airway Epithelial Cells Activate Dendritic Cells and Shape Their Microenvironment In Vitro},
  year         = {2016},
}