- Open Access
Zebrafish models of the immune response: taking it on the ChIn
© Renshaw and Ingham; licensee BioMed Central Ltd. 2010
- Received: 21 December 2010
- Accepted: 21 December 2010
- Published: 22 December 2010
The zebrafish is proving to be an extremely versatile new experimental model for unraveling the mysteries of innate immunity and has considerable promise as a system for the identification of novel modulators of this crucial biological process. A rate-limiting factor, however, is the mechanical stimulus required to induce the inflammatory response. A new chemically induced inflammation assay ('ChIn' assay) published in BMC Biology obviates this requirement and seems set to accelerate progress in the field.
- Transplant Cord Blood
- Zebrafish Larva
- Zebrafish Model
This innovation - which the authors call the chemically induced inflammation assay, or 'ChIn' assay for short - frees the neutrophil-recruitment model from the constraints imposed by manual intervention, thereby opening the door to the automation of both pharmacological and genetic screens. The zebrafish has been used for forward genetic analysis for more than 20 years, but more recently its suitability for pharmacological or 'chemical genetic' screens has become equally apparent . Such whole-organism screens provide a powerful approach to the discovery of biologically active compounds that can have utility either as reagents for the dissection of biological processes or as leads for the development of therapeutics. Indeed, the first compound identified in this type of zebrafish screen is currently in phase I clinical trials to improve engraftment of transplanted cord blood stem cells, and our own experience suggests that many more will follow. The ChIn protocol will now bring screens for modulators of the innate immune response within reach of many more labs than those with established expertise in the tailfin transection assay, allowing investigators studying the molecular basis of leukocyte recruitment and inflammation resolution to add the zebrafish model to their experimental armory.
While hypothesis-driven experiments are a crucial driver of scientific knowledge, the complementary benefits of unbiased screens are clear to see. Key advances in the field of innate immunity have been made by phenotype-driven approaches and the technological innovation of d'Alençon and colleagues should accelerate both the identification of novel genes underlying the innate immune response as well as novel therapeutic approaches to its manipulation. It is worth remembering that aspirin, one of the best selling anti-inflammatory drugs of all time, and the founding member of entire classes of medicines, was similarly identified by a phenotype: the ability to reduce fever.
The authors are supported by the UK MRC (SAR, Senior Clinical Fellowship, reference number: G0701932 and Centre grant G0700091), and by the Singapore Agency for Science Technology and Research (PWI).
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