Completed Infection & Immunity Lungs & Breathing

Innate lymphoid cells in immunity and disease.

Funder Wellcome Charity-funded
Recipient organisation Medical Research Council
Funding £2.1M
Period Oct 2013 — Sept 2020

In plain English

AI plain-English summary

The body’s immune system has a hidden layer of cells—innate lymphoid cells (ILCs)—that were only recently discovered and are now rewriting the textbook understanding of how the body fights infections and triggers autoimmune diseases. For decades, immunologists believed that T helper cells were the main conductors of the immune orchestra, releasing the signalling proteins called cytokines that coordinate attacks on parasites, bacteria, and viruses. But ILCs, which share many features with T cells yet lack their antigen-recognition machinery, turn out to be equally critical. They help clear parasitic worms (ILC2), fight bacterial infections (ILC1 and ILC3), and also drive inflammatory bowel disease and allergies when they go awry. The problem is that no one yet knows how these cells develop, how they relate to one another, or precisely which diseases they control. This project will map the developmental family tree of ILCs and test their roles in mouse models of infection and allergy. If successful, it could reveal new drug targets for conditions such as asthma, food allergy, and Crohn’s disease—offering alternatives to treatments that broadly suppress the immune system. This is fundamental science: the immediate payoff is a deeper understanding of how immunity works, not a therapy. But the discovery of ILCs themselves, only a decade ago, already shows how such foundational knowledge can open entirely new avenues for treating chronic inflammatory diseases.

View original technical description
Until very recently T helper cells (Th1, Th2, Th17) were thought to be the most significant source of cytokines for orchestrating immune responses. However, following the discovery of innate lymphoid cells (ILCs) by ourselves and others, we now know that these previously unappreciated cytokine-secreting ILC, including ILC1 (IFNg-expressing NK cells), ILC2 (IL-5 and IL-13-expressing nuocytes) and ILC3 (IL-22 and IL-17-expressing cells) are also critical regulators in protective immunity (against parasitic helminths (ILC2) and bacteria (ILC1 and ILC3)), but also in autoimmune disorders (e.g. IBD (ILC1 and ILC3) and allergy (ILC2)). ILCs form distinct sub-populations that share many characteristics with T helper cells, but do not express T cell receptor following VDJ recombination, and do not appear to respond directly to antigen stimulation. It is essential that we investigate the biological roles of ILCs to elucidate their developmental relationships within the lymphoid lineage an d their functional roles in protective immunity and disease. We wish to build on our existing knowledge of type-1 and type-2 disease models, and their dissection using molecular genetics in mice, to provide new insight into these pathways and identify potential therapeutic targets. Aim 1. To characterise the developmental relationship of innate lymphoid cells within the lymphoid lineage. Aim 2. To define the functional roles of type-2 innate lymphoid cells in protective immunity and disease. Aim 3. To identify and characterise novel cell subsets in type-2 immunity.

View the original record at the funder ↗

Researchers

Andrew McKenzie (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

Discovering new pathways of lymphocyte specification and function
Comprehensive analysis of plaque infiltrating ILC2 in human cardiovascular disease
The role of innate lymphoid cells in regulating intestinal inflammation
Characterization of innate lymphoid cells in intestinal pathophysiology.
The role of type 2 innate lymphoid cells in autoimmune islet infiltration and diabetes

Original classification

Investigator Award in Science

Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.