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

Hacini-Rachinel F, Gheit H, Le Luduec JB, Dif F, Nancey S, Kaiserlian D - PLoS ONE (2009)

Bottom Line: Probiotics are believed to alleviate allergic and inflammatory skin disorders, but their impact on pathogenic effector T cells remains poorly documented.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.

View Article: PubMed Central - PubMed

Affiliation: Université de Lyon, Lyon, France.

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 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.

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Effect of L. casei on CD8+ effectors and FoxP3+ regulatory T cells in the skin.Total cells were extracted from ears of either L. casei treated or NaCl mice that were either unsensitized, or DNFB-sensitized and harvested at 24 h, 48 h and 72 h post DNFB ear challenge. (A) Dot plot FACS analysis on gated CD45+ cells of ear cell suspensions staining for CD8 and granzyme B at 48 hr post challenge. (B) Histograms representation of the percentage of granzyme B+ CD8+ T cells (black portion) and granzyme B− CD8+: white portion) among gated CD45+ leucocytes from NaCl- (left) and L. Casei (right) treated mice at various time point after ear challenge. (C) Dot plot FACS analysis of gated CD45+×CD4+ T cells after ear cell suspensions stained for CD4, CD25 and FoxP3 at 48 hr post DNFB challenge in naïve (left) or sensitized (right) mice, treated with NaCl (top) or L. Casei (bottom). (D) Corresponding ear swelling at 24 h, 48 h and 72 h post- DNFB challenge in DNFB sensitized mice, treated with NaCl (white circles) or L. casei (black circles).
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pone-0004903-g003: Effect of L. casei on CD8+ effectors and FoxP3+ regulatory T cells in the skin.Total cells were extracted from ears of either L. casei treated or NaCl mice that were either unsensitized, or DNFB-sensitized and harvested at 24 h, 48 h and 72 h post DNFB ear challenge. (A) Dot plot FACS analysis on gated CD45+ cells of ear cell suspensions staining for CD8 and granzyme B at 48 hr post challenge. (B) Histograms representation of the percentage of granzyme B+ CD8+ T cells (black portion) and granzyme B− CD8+: white portion) among gated CD45+ leucocytes from NaCl- (left) and L. Casei (right) treated mice at various time point after ear challenge. (C) Dot plot FACS analysis of gated CD45+×CD4+ T cells after ear cell suspensions stained for CD4, CD25 and FoxP3 at 48 hr post DNFB challenge in naïve (left) or sensitized (right) mice, treated with NaCl (top) or L. Casei (bottom). (D) Corresponding ear swelling at 24 h, 48 h and 72 h post- DNFB challenge in DNFB sensitized mice, treated with NaCl (white circles) or L. casei (black circles).

Mentions: The efferent symptomatic phase of the CHS response induced upon challenge is initiated by the recruitment into the challenged skin site of primed CD8+ T cells, which initiate skin inflammation by inducing apoptosis of kératinocytes [17], [18]. We thus examined the outcome of L. casei treatment on the number and kinetics of accumulation of cytolytic granzyme B+ CD8+ effectors into the skin, at various time after hapten challenge. Irrespectively of L. casei treatment, CD8+ T cells were hardly detectable in the skin of NaCl-treated control unsensitized mice at 48 h post ear challenge (Fig 3A and B, left panels). Ear challenge of sensitized mice with the hapten resulted in the rapid recruitment of CD8+ T cells including both granzyme B+ and granzyme B− CD8+ CTL, which appeared within 24 hr after challenge and persisted for up to 72 hr (Fig 3Aupper right panel, and Fig 3Bleft). Interestingly, both granzyme B+ and granzyme B− subsets of CD8+ T cells were decreased in L. casei-treated mice (Fig 3Alower right panel, Fig 3Bright).


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

Hacini-Rachinel F, Gheit H, Le Luduec JB, Dif F, Nancey S, Kaiserlian D - PLoS ONE (2009)

Effect of L. casei on CD8+ effectors and FoxP3+ regulatory T cells in the skin.Total cells were extracted from ears of either L. casei treated or NaCl mice that were either unsensitized, or DNFB-sensitized and harvested at 24 h, 48 h and 72 h post DNFB ear challenge. (A) Dot plot FACS analysis on gated CD45+ cells of ear cell suspensions staining for CD8 and granzyme B at 48 hr post challenge. (B) Histograms representation of the percentage of granzyme B+ CD8+ T cells (black portion) and granzyme B− CD8+: white portion) among gated CD45+ leucocytes from NaCl- (left) and L. Casei (right) treated mice at various time point after ear challenge. (C) Dot plot FACS analysis of gated CD45+×CD4+ T cells after ear cell suspensions stained for CD4, CD25 and FoxP3 at 48 hr post DNFB challenge in naïve (left) or sensitized (right) mice, treated with NaCl (top) or L. Casei (bottom). (D) Corresponding ear swelling at 24 h, 48 h and 72 h post- DNFB challenge in DNFB sensitized mice, treated with NaCl (white circles) or L. casei (black circles).
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Related In: Results  -  Collection

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pone-0004903-g003: Effect of L. casei on CD8+ effectors and FoxP3+ regulatory T cells in the skin.Total cells were extracted from ears of either L. casei treated or NaCl mice that were either unsensitized, or DNFB-sensitized and harvested at 24 h, 48 h and 72 h post DNFB ear challenge. (A) Dot plot FACS analysis on gated CD45+ cells of ear cell suspensions staining for CD8 and granzyme B at 48 hr post challenge. (B) Histograms representation of the percentage of granzyme B+ CD8+ T cells (black portion) and granzyme B− CD8+: white portion) among gated CD45+ leucocytes from NaCl- (left) and L. Casei (right) treated mice at various time point after ear challenge. (C) Dot plot FACS analysis of gated CD45+×CD4+ T cells after ear cell suspensions stained for CD4, CD25 and FoxP3 at 48 hr post DNFB challenge in naïve (left) or sensitized (right) mice, treated with NaCl (top) or L. Casei (bottom). (D) Corresponding ear swelling at 24 h, 48 h and 72 h post- DNFB challenge in DNFB sensitized mice, treated with NaCl (white circles) or L. casei (black circles).
Mentions: The efferent symptomatic phase of the CHS response induced upon challenge is initiated by the recruitment into the challenged skin site of primed CD8+ T cells, which initiate skin inflammation by inducing apoptosis of kératinocytes [17], [18]. We thus examined the outcome of L. casei treatment on the number and kinetics of accumulation of cytolytic granzyme B+ CD8+ effectors into the skin, at various time after hapten challenge. Irrespectively of L. casei treatment, CD8+ T cells were hardly detectable in the skin of NaCl-treated control unsensitized mice at 48 h post ear challenge (Fig 3A and B, left panels). Ear challenge of sensitized mice with the hapten resulted in the rapid recruitment of CD8+ T cells including both granzyme B+ and granzyme B− CD8+ CTL, which appeared within 24 hr after challenge and persisted for up to 72 hr (Fig 3Aupper right panel, and Fig 3Bleft). Interestingly, both granzyme B+ and granzyme B− subsets of CD8+ T cells were decreased in L. casei-treated mice (Fig 3Alower right panel, Fig 3Bright).

Bottom Line: Probiotics are believed to alleviate allergic and inflammatory skin disorders, but their impact on pathogenic effector T cells remains poorly documented.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.

View Article: PubMed Central - PubMed

Affiliation: Université de Lyon, Lyon, France.

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 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.

Show MeSH
Related in: MedlinePlus