Inflammation induces dermal V?4+ ??T17 memory-like cells that travel to distant skin and accelerate secondary IL-17-driven responses.

ABSTRACT: Gamma delta (??) T cells represent a major IL-17 committed T-cell population (??T17 cells) in the mouse dermis. Following exposure to the inflammatory agent imiquimod (IMQ) the V?4(+) subset of ??T 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 ??T17 cells sensitize distant sites to inflammation has been unknown. Here we show that expanded V?4(+) ??T17 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 V?4(+) ??T cells upon imiquimod challenge. Transfer experiments confirm that memory-like V?4(+) ??T17 cells respond more rapidly. Memory-like V?4(+) ??T17 cells are distinguished by greater IL-1R1 expression and more proliferation in response to IL-1?. 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 ??T-cell population.

SUBMITTER: Ramirez-Valle F 

PROVIDER: S-EPMC4491769 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature