Investigating the biology of innate lymphoid cells at barrier sites and their draining lymphoid tissue

Dutton, Emma Elizabeth (2019). Investigating the biology of innate lymphoid cells at barrier sites and their draining lymphoid tissue. University of Birmingham. Ph.D.

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Abstract

Within this investigation a robust ILC identification method was used to identify ILCs and their subsets, comparing them across non-lymphoid and lymphoid tissues. ILCs were distributed differently across the analysed tissue and it was identified that surface marker expression, used to identify ILCs, was varied depending on location. The importance of digestion protocols was also highlighted, observing reduced expression of identification markers under harsher digestion protocols. Upon identifying ILCs, the role of the co-stimulatory molecule, inducible co-stimulator (ICOS), in their homeostasis was assessed. ILCs were not perturbed in the absence of ICOS:ICOSL interactions, suggesting a redundant role in ILC maintenance. This directed the aim of the investigation towards assessing ILC migration between non-lymphoid and lymphoid tissues. Photoconvertible Kaede mice were used to observe ILCs migration into peripheral LNs, with ILC1s likely entering in from the blood, in a CCR7-dependent manner. ILCs egressed from the LN in .an S1P-dependent manner and recirculated through contralateral LNs. Minimal ILC migration through the lymphatics was detected from the ear to the draining LN, however, was modestly increased under skin inflammation. Combined these data reveal fundamental new insight into the biology of ILCs at barrier sites and LNs, identifying a migratory population of ILCs.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):