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Body-barrier surveillance by epidermal γδ TCRs

Nature Immunology volume 13, pages 272–282 (2012)Cite this article

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An Erratum to this article was published on 18 May 2012

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Abstract

The surveillance of body barriers relies on resident T cells whose repertoires are biased toward particular γδ T cell antigen receptors (TCRs) according to location. These γδ TCRs can recognize ligands that emerge after stress. Through the use of intravital dynamics–immunosignal correlative microscopy, we found that γ-chain variable region 5 (Vγ5) TCRs expressed by epidermal T cells were constitutively clustered and functionally activated in vivo at steady state, forming true immunological synapses that polarized and anchored T cell projections at squamous keratinocyte tight junctions. This synaptogenesis depended on TCR variable domains, the kinase Lck and the integrin αEβ7 but not the γδ lineage or the receptor NKG2D. In response to tissue stress, TCR-proximal signals did not increase substantially but underwent stress mode–dependent relocalization toward the basal epidermis and Langerhans cells. Thus, the γδ TCR orchestrates barrier surveillance proactively, presumably by recognizing tissue ligands expressed in the steady state.

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Figure 1: DETCs are anchored in apical epidermis at steady state through PALPs in a manner dependent on Vγ5 TCRs.
Figure 2: DETCs in wild-type mice are targeted through the PALPs at squamous keratinocyte junctions dependent on γδ TCRs and independent of NKG2D.
Figure 3: Vγ5 TCRs are activated in PALPs and maintain DETCs in an activated state in vivo.
Figure 4: The γδ TCR mediates dendrite attachment through CD103.
Figure 5: PALPs show many hallmarks of immunological synapses.
Figure 6: The γδ TCR sustains dendrite outreach after trauma.
Figure 7: Tissue stress induces relocalization of TCR signals.
Figure 8: Redistribution of TCR signals toward the dermis and Langerhans cells in response to inflammatory stress.

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Change history

  • 04 April 2012

    In the version of this article initially published, the designation for DETCs that lack a Vγ5 TCR is incorrect. The correct designation is 'Vγ5-'. Also, on page 273, right column, second full paragraph, the designation for reporter mice in the first sentence is incorrect. The correct designation is 'IL-2p8–GFP'. The errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank W. Havran (The Scripps Research Institute) for the 7-17 cell line and advice; E. Rothenberg and M. Yui (Caltech) for IL-2p8–GFP mice; M. Nussenzweig (The Rockefeller University) for CD11c-YFP; L. Lanier, J. Beilke and M. Orr (University of California, San Francisco) for tissue samples from DAP10-DAP12–deficient mice; N.R.J. Gascoigne and G. Fu (The Scripps Research Institute), D. Zhou (MD Anderson Cancer Center) and W. Swat (Washington University School of Medicine) for other mutant mice (data not shown); A. Fukunaga for help with tissue processing; D. Nevozhay for help with statistical analysis; and M. Kripke, S. Watowich, C. Zhu, S. Ullrich, K. Newberry and W. Pagel for comments on the manuscript. Supported by the National Institute of Allergy and Infection Diseases (K22-AI065688 to T.Z.), MD Anderson Cancer Center (3-0026138 to T.Z.), the National Cancer Institute (CA016672 to MD Anderson) and institutional startup funds (T.Z.).

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Authors and Affiliations

  1. Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Grzegorz Chodaczek, Veena Papanna, M Anna Zal & Tomasz Zal

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  1. Grzegorz Chodaczek
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Contributions

G.C. and T.Z. designed the studies, analyzed and interpreted the results and wrote the manuscript; G.C. obtained most of the data; and V.P. and M.A.Z. assisted and acquired some of the data.

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Correspondence to Tomasz Zal.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–9 and Methods (PDF 6777 kb)

Supplementary Video 1

Apical dendrites are stably anchored. (MOV 992 kb)

Supplementary Video 2

Three-dimensional confocal visualization of DETCs forming apical PALPs in healthy epidermis. (MOV 14131 kb)

Supplementary Video 3

Intravital dynamics-immunosignal correlative microscopy shows that DETC dendrites are anchored in the apical epidermis through PALPs depending on γδTCR. (MOV 670 kb)

Supplementary Video 4

Anchoring of apical dendrites depends on γδ TCR. (MOV 6192 kb)

Supplementary Video 5

Anchoring of apical dendrites depends on Vγ5 TCR. (MOV 1560 kb)

Supplementary Video 6

DETCs remain anchored for days. (MOV 2493 kb)

Supplementary Video 7

DETC dynamics in response to stress stimuli. (MOV 3739 kb)

Supplementary Video 8

Skin inflammation after TLR9 stimulation induces redistribution of TCR signaling. (MOV 10656 kb)

Supplementary Video 9

DETC-Langerhans cell synapse. (MOV 489 kb)

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Chodaczek, G., Papanna, V., Zal, M. et al. Body-barrier surveillance by epidermal γδ TCRs. Nat Immunol 13, 272–282 (2012). https://doi.org/10.1038/ni.2240

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