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Chemokine-induced cutaneous inflammatory cell infiltration in a model of Hu-PBMC-SCID mice grafted with human skin

Chemokine-induced cutaneous inflammatory cell infiltration in a model of Hu-PBMC-SCID mice grafted with human skin
Chemokine-induced cutaneous inflammatory cell infiltration in a model of Hu-PBMC-SCID mice grafted with human skin
Recently, certain chemokines and chemokine receptors have been preferentially associated with the selective recruitment in vitro of type 1 T cells, such as IP-10 and its receptor CXCR3, or type 2 T cells such as monocyte-derived chemokine (MDC) and eotaxin and their receptors CCR4 and CCR3. Very few models have provided confirmation of these findings in vivo. Taking advantage of the humanized SCID mouse model grafted with autologous human skin, the ability of the chemokines IP-10, MDC, eotaxin, and RANTES to stimulate cell recruitment was investigated. Intradermal IP-10 injection resulted in an influx of CD4+ T lymphocytes but also surprisingly in the recruitment of dendritic cells. MDC recruited mainly CD8+ T lymphocytes, and had little effect on eosinophils. As predicted, eotaxin was a potent inducer of eosinophil and basophil migration, also recruiting CD4+ T cells.
RANTES, a ubiquitous chemokine associated with both type 1 and type 2 profiles, was able to recruit all cell types. CXCR3-positive cells were preferentially recruited by IP-10, whereas CCR3- and CCR4-positive cells were predominantly found after injection of eotaxin and MDC. Thus, in a human environment in vivo, some chemokines have the ability to recruit cells expressing chemokine receptors preferentially expressed on type 1 or type 2 cells. Further investigations revealed that MDC and eotaxin induced the recruitment of type 2, but not type 1, cytokine-producing cells. RANTES, on the other hand, induced the migration of both type 1 and type 2 cytokine-secreting cells, whereas IP-10 did not induce the recruitment of either subtype. These studies provide detailed information on the properties of MDC, eotaxin, IP-10, and RANTES as chemotactic molecules in skin in vivo. The use of the humanized SCID mouse model grafted with human skin is validated as a useful model for the evaluation of chemokine function in the inflammatory reaction, and suggests that therapeutic targeting of certain chemokines might be of interest in diseases associated preferentially with a type 1 or type 2 profile.
0002-9440
1053-1063
Fahy, Olivier
22c46d42-a3c3-4244-873d-76799b063dd3
Porte, Henri
73512290-e35f-460e-8aa8-e7d54f7f0687
Senechal, Stephanie
d709323e-8b9c-468e-8e1a-3430b15aa24e
Vorng, Han
f14c8853-5a82-442d-bfea-0f4814328a44
McEuen, Alan R.
e2054594-c27d-4d45-86ed-c899dc401c3a
Buckley, Mark G.
e4abc0c1-8413-4b27-bded-e94312c66424
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Wallaert, Benoit
8803e1ee-e17e-45bc-bcc1-9388dc9f0f99
Tonnel, André-Bernard
7bcb9d37-5a2f-4a9c-9933-f07996b4973e
Tsicopoulos, Anne
64f0aea3-5e44-4c2a-9f8e-76be79241fda
Fahy, Olivier
22c46d42-a3c3-4244-873d-76799b063dd3
Porte, Henri
73512290-e35f-460e-8aa8-e7d54f7f0687
Senechal, Stephanie
d709323e-8b9c-468e-8e1a-3430b15aa24e
Vorng, Han
f14c8853-5a82-442d-bfea-0f4814328a44
McEuen, Alan R.
e2054594-c27d-4d45-86ed-c899dc401c3a
Buckley, Mark G.
e4abc0c1-8413-4b27-bded-e94312c66424
Walls, Andrew F.
aaa7e455-0562-4b4c-94f5-ec29c74b1bfe
Wallaert, Benoit
8803e1ee-e17e-45bc-bcc1-9388dc9f0f99
Tonnel, André-Bernard
7bcb9d37-5a2f-4a9c-9933-f07996b4973e
Tsicopoulos, Anne
64f0aea3-5e44-4c2a-9f8e-76be79241fda

Fahy, Olivier, Porte, Henri, Senechal, Stephanie, Vorng, Han, McEuen, Alan R., Buckley, Mark G., Walls, Andrew F., Wallaert, Benoit, Tonnel, André-Bernard and Tsicopoulos, Anne (2001) Chemokine-induced cutaneous inflammatory cell infiltration in a model of Hu-PBMC-SCID mice grafted with human skin. The American Journal of Pathology, 158 (3), 1053-1063.

Record type: Article

Abstract

Recently, certain chemokines and chemokine receptors have been preferentially associated with the selective recruitment in vitro of type 1 T cells, such as IP-10 and its receptor CXCR3, or type 2 T cells such as monocyte-derived chemokine (MDC) and eotaxin and their receptors CCR4 and CCR3. Very few models have provided confirmation of these findings in vivo. Taking advantage of the humanized SCID mouse model grafted with autologous human skin, the ability of the chemokines IP-10, MDC, eotaxin, and RANTES to stimulate cell recruitment was investigated. Intradermal IP-10 injection resulted in an influx of CD4+ T lymphocytes but also surprisingly in the recruitment of dendritic cells. MDC recruited mainly CD8+ T lymphocytes, and had little effect on eosinophils. As predicted, eotaxin was a potent inducer of eosinophil and basophil migration, also recruiting CD4+ T cells.
RANTES, a ubiquitous chemokine associated with both type 1 and type 2 profiles, was able to recruit all cell types. CXCR3-positive cells were preferentially recruited by IP-10, whereas CCR3- and CCR4-positive cells were predominantly found after injection of eotaxin and MDC. Thus, in a human environment in vivo, some chemokines have the ability to recruit cells expressing chemokine receptors preferentially expressed on type 1 or type 2 cells. Further investigations revealed that MDC and eotaxin induced the recruitment of type 2, but not type 1, cytokine-producing cells. RANTES, on the other hand, induced the migration of both type 1 and type 2 cytokine-secreting cells, whereas IP-10 did not induce the recruitment of either subtype. These studies provide detailed information on the properties of MDC, eotaxin, IP-10, and RANTES as chemotactic molecules in skin in vivo. The use of the humanized SCID mouse model grafted with human skin is validated as a useful model for the evaluation of chemokine function in the inflammatory reaction, and suggests that therapeutic targeting of certain chemokines might be of interest in diseases associated preferentially with a type 1 or type 2 profile.

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Published date: 2001

Identifiers

Local EPrints ID: 27043
URI: http://eprints.soton.ac.uk/id/eprint/27043
ISSN: 0002-9440
PURE UUID: 4eb470da-7f39-44f8-8e86-2ed5d7ff58d1
ORCID for Andrew F. Walls: ORCID iD orcid.org/0000-0003-4803-4595

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Date deposited: 26 Apr 2006
Last modified: 23 Jul 2022 01:33

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Contributors

Author: Olivier Fahy
Author: Henri Porte
Author: Stephanie Senechal
Author: Han Vorng
Author: Alan R. McEuen
Author: Mark G. Buckley
Author: Andrew F. Walls ORCID iD
Author: Benoit Wallaert
Author: André-Bernard Tonnel
Author: Anne Tsicopoulos

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