Transgenic models of immune and haematopoietic disorders
Immune cells secrete a spectrum of interleukins, which play a critical role in regulating antibody production, inflammation and haematopoiesis. Dysregulation of these factors can lead to the manifestation of diseases such as asthma, autoimmunity and leukaemia. Our goal is to decipher how these interleukins interact in vivo during haematopoiesis and immune responses in order to provide insight into the complex networks created by these growth and differentiation factors, and suggest how they might be manipulated therapeutically.
Of special interest is a cluster of linked cytokine genes, on mouse chromosome 11 and human chromosome 5, encoding IL-4, IL-5, IL-9 and IL-13. These cytokines are central to the type-2 immune responses generated during asthma and allergic reactions, and various infections. We are currently investigating molecules that regulate the initiation of type-2 immunity. This work has led to the discovery of a new innate immune cell that we have termed the nuocyte. We have also demonstrated that blocking IL-25 prevents many of the features of asthma in experimental models and represents a new therapeutic target in asthma.
To understand the molecular regulation of these complex diseases we are using 'knockout' technologies and conventional transgenesis. These methodologies enable our manipulation of specific genes in mammalian experimental models of disease providing insight into basic immuno-regulatory mechanisms and identification of novel pathways for therapeutic intervention.
- Chang, Y.J., Kim, H.Y., Albacker, L.A., Baumgarth, N., McKenzie, A.N., Smith, D.E., Dekruyff, R.H. and Umetsu, D.T. (2011)
Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity.
Nat Immunol 12: (7):631-638.
- Neill, D.R., Wong, S.H., Bellosi, A., Flynn, R.J., Daly, M., Langford, T.K., Bucks, C., Kane, C.M., Fallon, P.G., Pannell, R., Jolin, H.E. and McKenzie, A.N. (2010)
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.
Nature 464: (7293):1367-70.
- Barlow, J.L., Drynan, L.F., Hewett, D.R., Holmes, L.R., Lorenzo-Abalde, S., Lane, A.L., Jolin, H.E., Pannell, R., Middleton, A.J., Wong, S.H., Warren, A.J., Wainscoat, J.S., Boultwood, J. and McKenzie, A.N. (2010)
A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.
Nat Med 16: (1):59-66.
- Helen Jolin
- Jillian Barlow
- Veera Panova
- Alfred Lim
- You Yi Hwang
- Paula Clark
- Jennifer Walker
- Seth Scanlon
- Tim Halim
- Alexandros Englezakis
- Batika Rana
- Martin Knolle