Abstract
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 IFNγ-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.
Highlights
Probiotics are defined by FAO and WHO as live microorganisms which when administered in adequate amounts, confer a health benefit to the host [1]
Lactic acid bacteria including bifidobacteria and lactobacilli used as probiotics are commensal bacteria of the gut microbiota that could be used for prevention or treatment of chronic allergic and inflammatory diseases, such as inflammatory bowel disease (IBD) [3] and atopic dermatitis [4]
We previously reported that oral administration of L. caseifermented milk reduces T cell-mediated delayed-type contact hypersensitivity (CHS) to the hapten 2-4-dinitrofluorobenzene (DNFB) in normal mice [11], which reproduces the pathophysiology of allergic contact dermatitis in human
Summary
Probiotics are defined by FAO and WHO as live microorganisms which when administered in adequate amounts, confer a health benefit to the host [1]. Administered probiotics exhibit widespread effects on gut homeostasis and immunomodulation of both mucosal and systemic immunity. Oral administration of a probiotic cocktail (VSL#3) composed of several lactic acid bacteria reduced the severity of chronic T-cell mediated TNBS induced-colitis in mice by acting via a subset of TGFß-bearing cells in the gut lamina propria [6]. In a recently developed mouse model of colitis mediated by cytotoxic CD8 T cells [8], we observed that L. casei DN-114 001 exerts a protective effect on the severity of intestinal lesions and enhances the function of mucosal CD4+ FoxP3+ Treg in the colon lamina propria (Hacini-Rachinel et al, submitted)
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