Nonhealing wounds are a major complication of diseases such as diabetes and rheumatoid arthritis. For efficient tissue repair, inflammatory cells must infiltrate into the damaged tissue to orchestrate wound closure. Hyaluronan is involved in the inflammation associated with wound repair and binds the surface of leukocytes infiltrating damaged sites. Skin γδ T cells play specialized roles in keratinocyte proliferation during wound repair. Here, we show that γδ T cells are required for hyaluronan deposition in the extracellular matrix (ECM) and subsequent macrophage infiltration into wound sites. We describe a novel mechanism of control in which γδ T cell–derived keratinocyte growth factors induce epithelial cell production of hyaluronan. In turn, hyaluronan recruits macrophages to the site of damage. These results demonstrate a novel function for skin γδ T cells in inflammation and provide a new perspective on T cell regulation of ECM molecules.
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18 April 2005
Article|
April 18 2005
γδ T cell–induced hyaluronan production by epithelial cells regulates inflammation
Julie M. Jameson,
Julie M. Jameson
The Scripps Research Institute, La Jolla, CA 92037
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Gabrielle Cauvi,
Gabrielle Cauvi
The Scripps Research Institute, La Jolla, CA 92037
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Leslie L. Sharp,
Leslie L. Sharp
The Scripps Research Institute, La Jolla, CA 92037
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Deborah A. Witherden,
Deborah A. Witherden
The Scripps Research Institute, La Jolla, CA 92037
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Wendy L. Havran
Wendy L. Havran
The Scripps Research Institute, La Jolla, CA 92037
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Julie M. Jameson
The Scripps Research Institute, La Jolla, CA 92037
Gabrielle Cauvi
The Scripps Research Institute, La Jolla, CA 92037
Leslie L. Sharp
The Scripps Research Institute, La Jolla, CA 92037
Deborah A. Witherden
The Scripps Research Institute, La Jolla, CA 92037
Wendy L. Havran
The Scripps Research Institute, La Jolla, CA 92037
CORRESPONDENCE Wendy L. Havran: [email protected]
The online version of this article contains supplemental material.
Abbreviations used: DETC, dendritic epidermal T cells; IEL, intraepithelial lymphocyte; ECM, extracellular matrix; GAG, glycosaminoglycan; HAS, hyaluronan synthases; FGF-7, keratinocyte growth factor-1; FGF-10, keratinocyte growth factor-2.
Received:
October 06 2004
Accepted:
March 07 2005
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2005
J Exp Med (2005) 201 (8): 1269–1279.
Article history
Received:
October 06 2004
Accepted:
March 07 2005
Citation
Julie M. Jameson, Gabrielle Cauvi, Leslie L. Sharp, Deborah A. Witherden, Wendy L. Havran; γδ T cell–induced hyaluronan production by epithelial cells regulates inflammation . J Exp Med 18 April 2005; 201 (8): 1269–1279. doi: https://doi.org/10.1084/jem.20042057
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