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Deficiency in IL-17-committed Vγ4+ γδ T cells in a spontaneous Sox13-mutant CD45.1+ congenic mouse substrain provides protection from dermatitis

Nature Immunology volume 14, pages 584592 (2013) | Download Citation

Abstract

Interleukin 17 (IL-17)-committed γδ T cells (γδT17 cells) participate in many immune responses, but their developmental requirements and subset specific functions remain poorly understood. Here we report that a commonly used CD45.1+ congenic C57BL/6 mouse substrain is characterized by selective deficiency in Vγ4+ γδT17 cells. This trait was due to a spontaneous mutation in the gene encoding the transcription factor Sox13 that caused an intrinsic defect in development of those cells in the neonatal thymus. The γδT17 cells migrated from skin to lymph nodes at low rates. In a model of psoriasis-like dermatitis, the Vγ4+ γδT17 cell subset expanded considerably in lymph nodes and homed to inflamed skin. Sox13-mutant mice were protected from psoriasis-like skin changes, which identified a role for Sox13-dependent γδT17 cells in this inflammatory condition.

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Acknowledgements

We thank A.-K. Hadjantonakis and S. Nowotschin (Memorial Sloan-Kettering) for making KikGR mice available; A. Weiss and K. Skrzypczynska (University of California San Francisco) for Ptprc−/− mice; L. Coussens (University of California San Francisco and Oregon Health Sciences University) for FVB/N mice; Q. Tang and A. Mahne (University of California San Francisco) for mice of the nonobese diabetic strain; A. Reboldi, Y. Han and J. Kang for discussions; and J. An for technical assistance. Supported by the US National Institutes of Health (T32 AR007175 to F.R.-V., and AI045073 to J.G.C.), the Dermatology Foundation (F.R.V.), the Biomedical Research Council (06/1/22/19/469 to Z.W. and K.E.K.) and the Howard Hughes Medical Institute (J.G.C.).

Author information

Affiliations

  1. Howard Hughes Medical Institute, University of California San Francisco, San Francisco, California, USA.

    • Elizabeth E Gray
    • , Francisco Ramírez-Valle
    • , Ying Xu
    • , Shuang Wu
    •  & Jason G Cyster
  2. Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California, USA.

    • Elizabeth E Gray
    • , Francisco Ramírez-Valle
    • , Ying Xu
    • , Shuang Wu
    •  & Jason G Cyster
  3. Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA.

    • Elizabeth E Gray
  4. Department of Dermatology, University of California San Francisco, San Francisco, California, USA.

    • Francisco Ramírez-Valle
  5. School of Biological Sciences, Nanyang Technological University, Singapore.

    • Zhihao Wu
    •  & Klaus E Karjalainen

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Contributions

E.E.G., F.R.-V. and J.G.C. designed the experiments; E.E.G. did most of the experiments; F.R.-V. and E.E.G. did the psoriasis experiments; Y.X. and S.W. did the gene-expression analysis; Z.W. and K.E.K. provided the antibody to SCART2; E.E.G., F.R.-V. and J.G.C. analyzed the data; and E.E.G. and J.G.C. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jason G Cyster.

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https://doi.org/10.1038/ni.2585

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