MRC Laboratory of Molecular Biology

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Home Group Leaders H to M Andrew McKenzie
Andrew McKenzie Andrew McKenzie

Transgenic models of immune and haematopoietic disorders

Chang YJ, Kim HY, Albacker LA, Baumgarth N, McKenzie AN, Smith DE, Dekruyff RH, Umetsu DT. (2011)
Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity.
Nat Immunol. 2011 May 29; 12(7):631-638.

Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN. (2010)
Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity.
Nature. 2010 Apr 29;464(7293):1367-70.

Barlow JL, Drynan LF, Hewett DR, Holmes LR, Lorenzo-Abalde S, Lane AL, Jolin HE, Pannell R, Middleton AJ, Wong SH, Warren AJ, Wainscoat JS, Boultwood J, McKenzie AN. (2010)
A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q- syndrome.
Nat Med. 2010 Jan;16(1):59-66.

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Group Members

  • Helen Jolin
  • Jillian Barlow
  • Eyal Arbely
  • Ana Camelo
  • Veera Panova
  • Clare Hardman
  • You Yi Hwang
  • Christopher Oliphant
  • Paula Clark
  • Jennifer Walker

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.

Engineered megabase deletion on  mouse chromosome 11
Engineered megabase deletion on
mouse chromosome 11

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.

Blocking IL-25 prevents mucus production (pink) in the airwaysBlocking IL-25 prevents mucus production (pink) in the airways

 

Last Updated on Friday, 15 July 2011 08:23