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Title: Investigating the role of defined microbes in modulating skin immune responses
Author: Suen, Victoria Melissa
ISNI:       0000 0004 7427 9278
Awarding Body: King's College London
Current Institution: King's College London (University of London)
Date of Award: 2018
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The skin represents the primary interface between the host and the external environment. It is home to an array of microorganisms that are crucial in maintaining homeostasis and controlling local immunity. Accumulating evidence suggests that skewing of microbial colonisation is critically linked to the development of different skin diseases such as atopic dermatitis (AD) and psoriasis. Among those S. aureus and C. simulans are of special interest for AD and psoriasis respectively, whereas L. crispatus appears to be relevant for healthy skin. However, little is known about how host-microbe interactions can trigger or regulate inflammatory processes in the skin. Dendritic cells (DCs) play a pivotal role in immunological responses and were therefore used in this study to explore the effect of key microbes on skin immunity. The aim of the project was to investigate the direct effects of defined microbes on different DC subsets and their indirect effects on adaptive immune responses. This study demonstrates that different DC subsets in skin exhibit unique immune responses to specific microbes. Langerhans cells were unresponsive to bacterial extracts whereas dermal DCs (DDCs) were more readily matured. Notably, CD141+ DDCs were the only subset to be activated by L. crispatus and produced a range of cytokines after bacterial stimulation. Next it was shown that DC priming with specific microbes, such as L. crispatus-primed CD141+ DDC-like DCs, could induce a distinct population of CD25+ FoxP3hi-expressing T cells, which was impaired in psoriasis patients. Despite phenotypic resemblance to T regulatory (Treg) cells, these cells failed to exhibit suppressive function. Functional specialisation of DC subsets could account for the compartmentalised host regulation of immunogenic or tolerogenic responses to skin microbes. Overall, cutaneous immune cells act in a coordinated manner with specific microbes to calibrate immune status with profound implications for homeostasis and skin disease.
Supervisor: Lombardi, Giovanna ; Nestle, Frank Oliver Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available