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Human Dendritic Cells and the Regulation of Allergic Immune Responses

In English

Författare

Summary, in English

Dendritic cells (DC) are a heterogeneous lineage of bone-marrow-derived leukocytes that serve as the link between innate and adaptive immunity. They are professional antigen-presenting cells that play an important protective and regulatory role in both health and disease. This thesis is based upon six original papers that deal with the function and transcription of human DCs, with focus on their role in the inflammatory immune responses, such as allergic rhinitis. Transcriptional profiling of DCs with microarrays has been an extensively utilized technique in the projects presented in this thesis. We have evaluated the gene expression profiles and functions of two in vitro models of human DCs, namely the monocyte-derived DCs and the differentiated cell line MUTZ-3, and the transcriptional regulation induced in these models by pro-inflammatory signals. We have also studied the effect of allergenic stimulation on the transcription and function of DCs derived from healthy and allergic individuals. Two allergens were used, the detergent enzyme lipase and grass pollen, to evaluate the direct effect on phenotype and gene expression of DCs in addition to the subsequent ability of allergen-challenged DCs to amplify and modify the autologous effector T cell response. We demonstrate that the transcriptional responses of DCs and effector T cells to allergenic stimulation are different between allergic and healthy individuals. These transcriptional profiles involved in the immune recognition of allergens will be further evaluated in order to understand the interplay between DCs and T cells in allergic rhinitis. Furthermore, in addition to the in vitro models studied, we have performed phenotypical and transcriptional characterizations of in vivo DCs isolated from peripheral blood and tonsillar tissue. We suggest that follicular DCs in tonsils may have previously unacknowledged costimulatory functions in the germinal center reaction, as they express CD137. An extensive transcriptional profiling of freshly sorted DC subsets from blood and tonsils identified DC-subset selective gene expression and pinpoint their relationships. We demonstrate innate specialization of these subsets and show that the environment in tonsils determines the transcriptional activity of myeloid DCs. In conclusion, these studies have provided insight in the transcription and phenotype of in vivo immature/mature DC populations as well as in the immune response induced by allergens or inflammatory signals.

Publiceringsår

2005

Språk

Engelska

Dokumenttyp

Doktorsavhandling

Förlag

Department of Immunotechnology, Lund University

Ämne

  • Immunology in the medical area

Nyckelord

  • serology
  • transplantation
  • Immunologi
  • serologi
  • Immunology
  • allergic rhinitis
  • inflammation
  • transcriptional profiling
  • T cells
  • Dendritic cells
  • microarray

Status

Published

Handledare

ISBN/ISSN/Övrigt

  • ISBN: 91-7422-074-8

Försvarsdatum

8 april 2005

Försvarstid

10:00

Försvarsplats

Segerfalkssalen, Wallenberg Neurocentrum, Sölvegatan 17, Lund

Opponent

  • Françoise Rousset (Dr)