Microarray analyses demonstrate the involvement of type I interferons in psoriasiform pathology development in D6-deficient mice

Helen M Baldwin; Kenneth Pallas; Vicky King; Thomas Jamieson; Clive S McKimmie; Robert J B Nibbs; José M Carballido; Marcus Jaritz; Antal Rot; Gerard J Graham

doi:10.1074/jbc.M113.491563

Microarray analyses demonstrate the involvement of type I interferons in psoriasiform pathology development in D6-deficient mice

Helen M Baldwin, Kenneth Pallas, Vicky King, Thomas Jamieson, Clive S McKimmie, Robert J B Nibbs, José M Carballido, Marcus Jaritz, Antal Rot, Gerard J Graham

Research output: Contribution to journal › Article › peer-review

Abstract

The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes.

Original language	English
Pages (from-to)	36473-36483
Number of pages	11
Journal	The Journal of biological chemistry
Volume	288
Issue number	51
DOIs	https://doi.org/10.1074/jbc.M113.491563
Publication status	Published - 20 Dec 2013

Keywords

Animals
Female
Inflammation
Interferon Type I
Mice
Mice, Inbred C57BL
Mice, Knockout
Oligonucleotide Array Sequence Analysis
Phorbol Esters
Psoriasis
Receptors, CCR10
Transcription, Genetic

Access to Document

10.1074/jbc.M113.491563

Cite this

Baldwin, H. M., Pallas, K., King, V., Jamieson, T., McKimmie, C. S., Nibbs, R. J. B., Carballido, J. M., Jaritz, M., Rot, A., & Graham, G. J. (2013). Microarray analyses demonstrate the involvement of type I interferons in psoriasiform pathology development in D6-deficient mice. The Journal of biological chemistry, 288(51), 36473-36483. https://doi.org/10.1074/jbc.M113.491563

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abstract = "The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes.",

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AU - King, Vicky

AU - Jamieson, Thomas

AU - McKimmie, Clive S

AU - Nibbs, Robert J B

AU - Carballido, José M

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AU - Graham, Gerard J

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AB - The inflammatory response is normally limited by mechanisms regulating its resolution. In the absence of resolution, inflammatory pathologies can emerge, resulting in substantial morbidity and mortality. We have been studying the D6 chemokine scavenging receptor, which played an indispensable role in the resolution phase of inflammatory responses and does so by facilitating removal of inflammatory CC chemokines. In D6-deficient mice, otherwise innocuous cutaneous inflammatory stimuli induce a grossly exaggerated inflammatory response that bears many similarities to human psoriasis. In the present study, we have used transcriptomic approaches to define the molecular make up of this response. The data presented highlight potential roles for a number of cytokines in initiating and maintaining the psoriasis-like pathology. Most compellingly, we provide data indicating a key role for the type I interferon pathway in the emergence of this pathology. Neutralizing antibodies to type I interferons are able to ameliorate the psoriasis-like pathology, confirming a role in its development. Comparison of transcriptional data generated from this mouse model with equivalent data obtained from human psoriasis further demonstrates the strong similarities between the experimental and clinical systems. As such, the transcriptional data obtained in this preclinical model provide insights into the cytokine network active in exaggerated inflammatory responses and offer an excellent tool to evaluate the efficacy of compounds designed to therapeutically interfere with inflammatory processes.

KW - Animals

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KW - Inflammation

KW - Interferon Type I

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KW - Mice, Inbred C57BL

KW - Mice, Knockout

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KW - Phorbol Esters

KW - Psoriasis

KW - Receptors, CCR10

KW - Transcription, Genetic

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