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Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1

Nature Immunology volume 6, pages 73–79 (2005)Cite this article

Abstract

A fine balance between rates of proliferation and apoptosis in the skin provides a defensive barrier and a mechanism for tissue repair after damage. Vγ3+ dendritic epidermal T cells (DETCs) are primary modulators of skin immune responses. Here we show that DETCs both produce and respond to insulin-like growth factor 1 (IGF-1) after T cell receptor stimulation. Mice deficient in DETCs had a notable increase in epidermal apoptosis that was abrogated by the addition of DETCs or IGF-1. Furthermore, DETC-deficient mice had reduced IGF-1 receptor activation at wound sites. These findings indicate critical functions for DETC-mediated IGF-1 production in regulating skin homeostasis and repair.

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Figure 1: IGF-1R is expressed by DETCs after TCR stimulation.
Figure 2: DETCs express IGF-1 after TCR stimulation.
Figure 3: DETCs treated with IGF-1 are resistant to apoptosis.
Figure 4: Skin lacking DETCs has increased epidermal apoptosis.
Figure 5: Increased epidermal apoptosis in DETC-deficient skin is prevented by coculture with DETCs or growth factors.
Figure 6: TCRδ-deficient mice have reduced IGF-1R phosphorylation at wound sites.

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Acknowledgements

J. Barcas and A. Mayday provided technical assistance, and M. Carson, H.K. Komori, T. Meehan, D. Page and D. Witherden provided critical reading of the manuscript. Supported by the Leukemia and Lymphoma Society and National Institutes of Health (T32AI07244 and AI36964). This is manuscript number 16741-IMM from The Scripps Research Institute.

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  1. Leslie L Sharp and Julie M Jameson: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Immunology, The Scripps Research Institute, La Jolla, 92037, California, USA

    Leslie L Sharp, Julie M Jameson, Gabrielle Cauvi & Wendy L Havran

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  1. Leslie L Sharp
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Correspondence to Wendy L Havran.

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Sharp, L., Jameson, J., Cauvi, G. et al. Dendritic epidermal T cells regulate skin homeostasis through local production of insulin-like growth factor 1. Nat Immunol 6, 73–79 (2005). https://doi.org/10.1038/ni1152

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