Investigating the role of innate lymphoid cells in secondary lymphoid tissue

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Mackley, Emma Christine (2016). Investigating the role of innate lymphoid cells in secondary lymphoid tissue. University of Birmingham. Ph.D.

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Abstract

Innate lymphoid cells (ILCs) are an emerging family of cells which have been well-characterised within the gut and peripheral tissues. Despite being implicated in shaping adaptive immune responses, relatively little is known about their function within lymph nodes (LNs), important sites for the generation of this type of response. The aim of this investigation was to characterise ILC populations within a range of different LNs, both at steady state and using a draining LN model to understand their role in an immune response. Mice in which a subset of ILC, or key functional molecules, are deficient will be used to better understand their function within LNs, with a focus on adaptive immune responses.

My results reveal that ILCs are present in all LNs analysed, however, differences in the ILC composition of mucosal tissue and peripheral tissue-draining LNs indicate site-specific requirements for these cells. Differing dependencies on CCR7 for ILC entry into LNs were observed, consistent with migration of these cells into these secondary lymphoid tissues. Within LNs, group 3 ILCs were found to express major-histocompatibility complex class-II and specifically locate to sites where adaptive immune responses are initiated and maintained. Notably, ILCs accumulated in draining LNs following immunisation and whilst their roles here remain unclear they are unlikely to be involved in the priming of naïve CD4+ T cells. In summary, I show that subsets of ILC3 are enriched in LNs which drain mucosal sites and can be found to locate to crucial sites within LNs following their entry by a CCR7-dependent mechanism. These data support a role for ILC3 in adaptive immune responses.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):