The anatomical origins of migratory dendritic cells in the intestine

Houston, Stephanie Ailsa (2013) The anatomical origins of migratory dendritic cells in the intestine. PhD thesis, University of Glasgow.

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Abstract

The intestine is exposed to a vast array of harmless dietary antigen as well as an enormous community of commensal bacteria. Alongside this harmless antigen, pathogens can enter the body via the intestinal mucosal surface. The intestinal immune system must discriminate between pathogens and innocuous antigens. Dendritic cells (DCs), present in the small intestine (SI) and colon, are fundamental in controlling intestinal immune responses; they migrate to the mesenteric lymph node (MLN) and prime effector or regulatory T cells. Furthermore, DCs direct the immune response in the gut-associated lymphoid tissues (GALT), the Peyer’s patches (PP) and isolated lymphoid follicles (ILFs). The aim of this work was to determine the anatomical origins of DCs in the MLN. First, the anatomical organisation of lymphatic vessels draining to the MLN from the SI and colon was investigated. Second, DC migration in mice lacking specific GALT was explored. Finally, the migration of DCs from PPs to the MLN was investigated. To achieve these aims, DC migration was studied using a variety of labelling methods, mice that lacked specific GALT were employed, and surgical procedures were used to collect DCs from the thoracic duct. Here, I demonstrate the anatomical segregation of DCs that migrate to the MLN from the SI and colon. This was reflected in differences in DC subset composition and antigen presentation in the SI and colon-draining nodes of the MLN. Separate analysis of MLN nodes will allow a more refined understanding of intestinal immune responses. All but one DC subset, CD103-CD11b- DCs, were still present in pseudo-afferent lymph from mice lacking both PPs and ILFs. This subset is therefore likely to originate from either PPs or ILFs. Surprisingly, CD103+CD8α+ DCs were present in these mice, showing that many CD8α+ DCs were resident in the lamina propria and are not limited to lymphoid tissue. Four DC subsets are able to migrate from the intestine in PP-null mice, suggesting that CD103-CD11b- DCs migrate specifically from ILFs. I then demonstrated that DCs migrate from PPs to the MLN. These migrating PP DCs expanded in response to a DC specific growth factor and their migration depended on CCR7 and S1P. These cells may play an important role in driving immune responses in the MLN and their manipulation could lead to advances in controlling intestinal immune responses.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Dendritic cell, small intestine, colon, Peyer's patch, migration.
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Funder's Name: UNSPECIFIED
Supervisor's Name: Milling, Dr. Simon W.
Date of Award: 2013
Depositing User: Dr Stephanie Houston
Unique ID: glathesis:2013-5265
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jun 2014 14:05
Last Modified: 30 Jun 2017 15:19
URI: http://theses.gla.ac.uk/id/eprint/5265

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