Regulation of the immune system is fundamental to protecting the host from infection whilst constraining autoimmunity, undesirable inflammation and immunopathology. Immune dysregulation can lead to diseases such as asthma and allergy (Figure 1), autoimmunity and leukaemia.
Using techniques including mouse genetics, fluorescence imaging and gene expression analysis we discovered group 2 innate lymphoid cells (ILC2s) as significant new participants in immune regulation through their cytokine secretion (Figure 2). We now know that ILC2s belong to a larger family of ILCs that develop from lymphoid precursors that also give rise to the T and B cell lineages. We aim to identify the transcriptional pathways that regulate this differentiation and gain molecular insight into cell commitment.
ILC2s localise predominantly at mucosal surfaces where they act as critical sentinels for tissue damage and infection, at the interface of innate and adaptive immunity. Our goal is to determine the cellular and molecular pathways that regulate ILCs during homeostasis and disease, and how they might be targeted therapeutically in humans.
Selected Papers
- 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 - Clark, P.A., Gogoi, M., Rodriguez-Rodriguez, N., Ferreira, A.C.F., Murphy, J.E., Walker, J.A., Crisp, A., Jolin, H.E., Shields, J.D., McKenzie, A.N.J. (2024)
Recipient tissue microenvironment determines developmental path of intestinal innate lymphoid progenitors
Nat Commun 15(1): 7809 - Ferreira ACF, Szeto ACH, Clark PA, Crisp A, Kozik P, Jolin HE, McKenzie ANJ (2023)
Neuroprotective protein ADNP-dependent histone remodeling complex promotes T helper 2 immune cell differentiation.
Immunity - Szeto ACH, Ferreira ACF, Mannion J, Clark PA, Sivasubramaniam M, Heycock MWD, Crisp A, Jolin HE, Kozik P, Knolle MD, McKenzie ANJ. (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 AF, Jolin HE, Clark PA, Sawmynaden K, Ko M, Murphy JE, Mannion J, Ward C, Matthews DJ, Buczacki SJA, McKenzie ANJ. (2022)
An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis.
Sci Immunol. 7(72): eabn0175 - Rodriguez-Rodriguez N, Clark PA, Gogoi M, Ferreira ACF, Kerscher B, Crisp A, Jolin HE, Murphy JE, Sivasubramaniam M, Pedro L, Walker JA, Heycock MWD, Shields JD, Barlow JL, McKenzie ANJ. (2022)
Identification of aceNKPs, a committed common progenitor population of the ILC1 and NK cell continuum.
Proc Natl Acad Sci U S A. 119(49): e2203454119 - Ferreira ACF, Szeto ACH, Heycock MWD, Clark PA, Walker JA, Crisp A, Barlow JL, Kitching S, Lim A, Gogoi M, Berks R, Daly M, Jolin HE, McKenzie ANJ. (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., Cruz Migoni S., 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. 16(9): 1999-2009. - Walker J.A., Clark P.A., Crisp A., Barlow J.L., Szeto A., Ferreira A.C.F., Rana B.M.J., Jolin H.E., Rodriguez-Rodriguez N., Sivasubramaniam M., Pannell R., Cruickshank J., Daly M., Haim-Vilmovsky L., Teichmann S.A., McKenzie A.N.J. (2019)
Polychromic Reporter Mice Reveal Unappreciated Innate Lymphoid Cell Progenitor Heterogeneity and Elusive ILC3 Progenitors in Bone Marrow.
Immunity. 51(1): 104-118.
Group Members
- Pratiksha Bhat
- Paula Clark
- Ana Carolina Ferreira
- Mayuri Gogoi
- Emma Griffiths
- Helen Jolin
- Michelle Ko
- Shi Lu Luan
- Ntombizodwa (Tombi) Makuyana
- Molly Stevenson
- Aydan Szeto