Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2015 Jun 30;112(26):8046-51. doi: 10.1073/pnas.1508990112. Epub 2015 Jun 15.

Inflammation induces dermal Vγ4+ γδT17 memory-like cells that travel to distant skin and accelerate secondary IL-17-driven responses.

Author information

1
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; Department of Dermatology, University of California, San Francisco, CA 94143;
2
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143;
3
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143; Howard Hughes Medical Institute, University of California, San Francisco, CA 94143 jason.cyster@ucsf.edu.

Abstract

Gamma delta (γδ) T cells represent a major IL-17 committed T-cell population (γδT17 cells) in the mouse dermis. Following exposure to the inflammatory agent imiquimod (IMQ) the Vγ4(+) subset of γδT cells produce IL-17 in the skin and expand rapidly in draining lymph nodes (LNs). Local IMQ treatment in humans is known to exacerbate psoriasis skin lesion activity at distant sites. Whether expanded γδT17 cells sensitize distant sites to inflammation has been unknown. Here we show that expanded Vγ4(+) γδT17 cells egress from LNs in a fingolimod (FTY720)-sensitive manner and use C-C chemokine receptor type 2 to accumulate in inflamed skin where they augment neutrophil recruitment and inflammation. They also travel to noninflamed skin and peripheral LNs and remain in elevated numbers at these distant sites for at least 3 mo. Sensitized mice show more rapid skin inflammation and greater proliferation and IL-17 production by Vγ4(+) γδT cells upon imiquimod challenge. Transfer experiments confirm that memory-like Vγ4(+) γδT17 cells respond more rapidly. Memory-like Vγ4(+) γδT17 cells are distinguished by greater IL-1R1 expression and more proliferation in response to IL-1β. These findings establish that local skin inflammation leads to faster and stronger secondary responses to the same stimulus through long-term and systemic changes in the composition and properties of the dermal γδT-cell population.

KEYWORDS:

immunological memory; inflammation; γδT cells

PMID:
26080440
PMCID:
PMC4491769
DOI:
10.1073/pnas.1508990112
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center