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.

Within mucosal tissues innate lymphoid cells (ILCs) act as sentinels to help maintain tissue homeostasis and as an early warning system in response to tissue damage and infection. ILC2s play key roles at the interface between the local tissue microenvironment and the development of bespoke innate and adaptive immune reactions (see refs below).  When dysregulated they can lead to asthma and allergic responses and suppress immunity to cancer.

To investigate and understand such complex pathways of inflammation and immunity we leverage state-of-the-art techniques and develop new experimental models (see refs below). The project will involve determining the inter- and intra-cellular pathways which regulate immune cells within tissue-specific stromal and neural cell microenvironments.

Techniques: immunology-related assays, experimental models of disease, development and analysis of novel transgenic models, flow cytometry, single cell analysis – RNAseq, ATACseq, cell and tissue imaging, CRISPR/Cas9 techniques including unbiased CRISPR screens, bioinformatics.

References

Gogoi, M., Clark, P.A., Ferreira, A.C.F., Rodriguez, N.R., Heycock, M., Ko, M., Murphy, J.E., Chen, V., Luan, S., Jolin, H.E., McKenzie, A.N.J. (2024)
ILC2-derived LIF licences progress from tissue to systemic immunity
Nature 632(8026): 885-892

Szeto, A.C.H., Clark, P.A., Ferreira, A.C.F., Heycock, M., Griffiths, E.L., Jou, E., Mannion, J., Luan, S., Storrar, S., Knolle, M.D., Kozik, P., Jolin, H.E., Fallon, P.G., McKenzie, A.N.J. (2024)
Mef2d potentiates type-2 immune responses and allergic lung inflammation
Science 384(6703): eadl0370

Ferreira, A.C.F., Szeto, A.C.H., Clark, P.A., Crisp, A., Kozik, P., Jolin, H.E., McKenzie, A.N.J. (2023)
Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation
Immunity 56(7): 1468-1484

Szeto, A.C.H., Ferreira, A.C.F., Mannion, J., Clark, P.A., Sivasubramaniam, M., Heycock, M.W.D., Crisp, A., Jolin, H.E., Kozik, P., Knolle, M.D., McKenzie, A.N.J. (2023)
An αvβ3 integrin checkpoint is critical for efficient TH2 cell cytokine polarization and potentiation of antigen-specific immunity
Nat Immunol 24(1): 123-135

Jou, E., Rodriguez-Rodriguez, N., Ferreira, A.F., Jolin, H.E., Clark, P.A., Sawmynaden, K., Ko, M., Murphy, J.E., Mannion, J., Ward, C., Matthews, D.J., Buczacki, S.J.A., McKenzie, A.N.J. (2022)
An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis
Sci Immunol 7(72): eabn0175

Ferreira, A.C.F., Szeto, A.C.H., Heycock, M.W.D., Clark, P.A., Walker, J.A., Crisp, A., Barlow, J.L., Kitching, S., Lim, A., Gogoi, M., Berks, R., Daly, M., Jolin, H.E., McKenzie, A.N.J. (2021)
RORα is a critical checkpoint for T cell and ILC2 commitment in the embryonic thymus
Nat Immunol 22(2): 166-178

Rana, B.M.J., Jou, E., Barlow, J.L., Rodriguez-Rodriguez, N., Walker, J.A., Knox, C., Jolin, H.E., Hardman, C.S., Sivasubramaniam, M., Szeto, A., Cohen, E.S., Scott, I.C., Sleeman, M.A., Chidomere, C.I., Migoni, S.C., Caamano, J., Jorgensen, H.F., Carobbio, S., Vidal-Puig, A., McKenzie, A.N.J. (2019)
A stromal cell niche sustains ILC2-mediated type-2 conditioning in adipose tissue
J Exp Med 216(9): 1999-2009