Oral probiotic control skin inflammation by acting on both effector and regulatory T cells

Probiotics are believed to alleviate allergic and inflammatory skin disorders, but their impact on pathogenic effector T cells remains poorly documented. Here we show that oral treatment with the probiotic bacteria L. casei (DN-114 001) alone alleviates antigen-specific skin inflammation mediated by either protein-specific CD4(+) T cells or hapten-specific CD8(+) T cells. In the model of CD8(+) T cell-mediated skin inflammation, which reproduces allergic contact dermatitis in human, inhibition of skin inflammation by L. casei is not due to impaired priming of hapten-specific IFNgamma-producing cytolytic CD8(+) effector T cells. Alternatively, L. casei treatment reduces the recruitment of CD8(+) effector T cells into the skin during the elicitation (i.e. symptomatic) phase of CHS. Inhibition of skin inflammation by L. casei requires MHC class II-restricted CD4(+) T cells but not CD1d-restricted NK-T cells. L casei treatment enhanced the frequency of FoxP3(+) Treg in the skin and increased the production of IL-10 by CD4(+)CD25(+) regulatory T cells in skin draining lymph nodes of hapten-sensitized mice. These data demonstrate that orally administered L. casei (DN-114 001) efficiently alleviate T cell-mediated skin inflammation without causing immune suppression, via mechanisms that include control of CD8(+) effector T cells and involve regulatory CD4(+) T cells. L. casei (DN-114 001) may thus represent a probiotic of potential interest for immunomodulation of T cell-mediated allergic skin diseases in human.