The role of innate lymphoid cells at the interface of the immune and nervous systems
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Regulation of the immune system is fundamental to protecting the host from infection whilst also constraining inappropriate responses that may lead to autoimmunity and undesirable inflammation and immunopathology.
We discovered group 2 innate lymphoid cells (ILC2s) as significant new participants in type-2 immune regulation (asthma and allergic responses). These cells belong to a larger family of ILCs that develop from a novel ILC precursor. ILCs localise predominantly at mucosal surfaces where they act as critical innate sentinels for tissue damage and infection at the boundary of innate and adaptive immunity.
Interestingly, we have identified that restricted subsets of ILCs selectively express receptors for neurotransmitters and neuropeptides. This raises the possibility that tissue resident ILCs may play key roles in interacting with the nervous system during homeostasis, and responses to injury and infection. We wish to identify the functional importance of ILC-expressed neuro-regulators in inflammation and immunity.
This project will involve using CRISPR/Cas9 technologies to generate gene-modified mice in which specific neuromodulators can be deleted in specific ILC subsets. These can then be tested in mouse models of allergy and asthma, and infection.
This work has the potential for identifying new therapeutic targets for asthma and allergy.
The student will gain skills in immunology, whole organism physiology (an MRC skill priority), flow cytometry, single cell analysis - RNAseq, CRISPR/Cas9 techniques, bioinformatics.
Eberl, G., Colonna, M., Di Santo, J.P. and McKenzie, A.N. (2015)
Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology.
Science. May 22;348(6237):aaa6566.
McKenzie, A.N., Spits, H. and Eberl, G. (2014)
Innate lymphoid cells in inflammation and immunity.
Immunity. Sep 18;41(3):366-74
Cardoso V, Chesné J, Ribeiro H, García-Cassani B, Carvalho T, Bouchery T, Shah K, Barbosa-Morais NL, Harris N, Veiga-Fernandes H. (2017)
Neuronal regulation of type 2 innate lymphoid cells via neuromedin U.
Nature. 2017 Sep doi: 10.1038/nature23469. [Epub ahead of print] PMID: 28869974