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Nat Commun. 2014 Jun 9;5:3986. doi: 10.1038/ncomms4986.

Differential developmental requirement and peripheral regulation for dermal Vγ4 and Vγ6T17 cells in health and inflammation.

Author information

1
1] James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA [2].
2
1] Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China [2].
3
James Graham Brown Cancer Center, Department of Medicine and Department of Microbiology and Immunology, University of Louisville, Louisville, Kentucky 40202, USA.
4
Center for Molecular Immunology and Infectious Diseases and Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
5
Department of Dermatology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China.

Abstract

Dermal IL-17-producing γδT cells have a critical role in skin inflammation. However, their development and peripheral regulation have not been fully elucidated. Here we demonstrate that dermal γδT cells develop from the embryonic thymus and undergo homeostatic proliferation after birth with diversified TCR repertoire. Vγ6T cells are bona fide resident, but precursors of dermal Vγ4T cells may require extrathymic environment for imprinting skin-homing properties. Thymic Vγ6T cells are more competitive than Vγ4 for dermal γδT cell reconstitution and TCRδ(-/-) mice reconstituted with Vγ6 develop psoriasis-like inflammation after IMQ-application. Although both IL-23 and IL-1β promote Vγ4 and Vγ6 proliferation, Vγ4 are the main source of IL-17 production that requires IL-1 signalling. Mice with deficiency of IL-1RI signalling have significantly decreased skin inflammation. These studies reveal a differential developmental requirement and peripheral regulation for dermal Vγ6 and Vγ4 γδT cells, implying a new mechanism that may be involved in skin inflammation.

PMID:
24909159
PMCID:
PMC4068267
DOI:
10.1038/ncomms4986
[Indexed for MEDLINE]
Free PMC Article

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