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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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In vivo suppressive function of CD4+CD25+ Tregs from L. casei-treated mice.(A) Naïve C57Bl/6 were treated daily from d-14 to d-1 with either L. casei or NaCl. On d-1, CD4+ CD25+ T cells were purified from pooled pLN, mLN and spleens of each group of mice and transferred i.v together with naive purified CD8+ T cells into naive CD3ε°/° recipients. On day 0, untransferred and transferred CD3ε°/° recipients were DNFB-sensitized and challenged 5 days later with DNFB, as described in Fig 1 legend. (B) Ear swelling was determined at various time after challenge in CD3ε°/° that were either untransferred (dotted lines) or transferred with CD8+ T cells alone (white squares), or with CD8+ T cells together with CD4+CD25+ T cells from L. casei- treated (black circle) or NaCl-treated (empty circles) donors.
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pone-0004903-g006: In vivo suppressive function of CD4+CD25+ Tregs from L. casei-treated mice.(A) Naïve C57Bl/6 were treated daily from d-14 to d-1 with either L. casei or NaCl. On d-1, CD4+ CD25+ T cells were purified from pooled pLN, mLN and spleens of each group of mice and transferred i.v together with naive purified CD8+ T cells into naive CD3ε°/° recipients. On day 0, untransferred and transferred CD3ε°/° recipients were DNFB-sensitized and challenged 5 days later with DNFB, as described in Fig 1 legend. (B) Ear swelling was determined at various time after challenge in CD3ε°/° that were either untransferred (dotted lines) or transferred with CD8+ T cells alone (white squares), or with CD8+ T cells together with CD4+CD25+ T cells from L. casei- treated (black circle) or NaCl-treated (empty circles) donors.

Mentions: To determine whether L. casei treatment affected the pool of natural CD4+CD25+ Tregs of lymphoid organs at the steady state (i.e. unsentitized mice), we set up an adoptive co-transfer model of CD4+CD25+ Tregs and CD8+ T cell into T cell deficient CD3ε°/° mice. MACS-sorted CD4+CD25+ T cells harvested from naive C57Bl/6 donor mice treated by daily oral administration of L. casei or NaCl as control for 14 days, were co-transferred with CD8+ T cells from naive C57Bl/6 into syngenic CD3ε°/° recipients one day before skin sensitization and the CHS response to DNFB was examined after ear challenge with DNFB (Fig 6A). As described above (Fig 4B), CD3ε°/° recipient mice mounted a CHS response to DNFB only upon CD8 reconstitution, with a mean ear swelling of 330 µm±85 at day 4 after challenge, that was sustained for up to day 9 (Fig 6B). Co-transfer of Tregs cells from either NaCl- or L. casei- treated donors resulted in a similar 30% (p = 0.0076) reduction of skin inflammation with mean ear swelling values at 96 hr post challenge of 220 µm±92 and 230 µm±57, respectively. These data demonstrate that daily oral exposure to L. casei in a naive host is not capable to affect the potential of natural CD4+ CD25+ Treg of lymphoid organs to suppress a CHS response.


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)

In vivo suppressive function of CD4+CD25+ Tregs from L. casei-treated mice.(A) Naïve C57Bl/6 were treated daily from d-14 to d-1 with either L. casei or NaCl. On d-1, CD4+ CD25+ T cells were purified from pooled pLN, mLN and spleens of each group of mice and transferred i.v together with naive purified CD8+ T cells into naive CD3ε°/° recipients. On day 0, untransferred and transferred CD3ε°/° recipients were DNFB-sensitized and challenged 5 days later with DNFB, as described in Fig 1 legend. (B) Ear swelling was determined at various time after challenge in CD3ε°/° that were either untransferred (dotted lines) or transferred with CD8+ T cells alone (white squares), or with CD8+ T cells together with CD4+CD25+ T cells from L. casei- treated (black circle) or NaCl-treated (empty circles) donors.
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Related In: Results  -  Collection

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pone-0004903-g006: In vivo suppressive function of CD4+CD25+ Tregs from L. casei-treated mice.(A) Naïve C57Bl/6 were treated daily from d-14 to d-1 with either L. casei or NaCl. On d-1, CD4+ CD25+ T cells were purified from pooled pLN, mLN and spleens of each group of mice and transferred i.v together with naive purified CD8+ T cells into naive CD3ε°/° recipients. On day 0, untransferred and transferred CD3ε°/° recipients were DNFB-sensitized and challenged 5 days later with DNFB, as described in Fig 1 legend. (B) Ear swelling was determined at various time after challenge in CD3ε°/° that were either untransferred (dotted lines) or transferred with CD8+ T cells alone (white squares), or with CD8+ T cells together with CD4+CD25+ T cells from L. casei- treated (black circle) or NaCl-treated (empty circles) donors.
Mentions: To determine whether L. casei treatment affected the pool of natural CD4+CD25+ Tregs of lymphoid organs at the steady state (i.e. unsentitized mice), we set up an adoptive co-transfer model of CD4+CD25+ Tregs and CD8+ T cell into T cell deficient CD3ε°/° mice. MACS-sorted CD4+CD25+ T cells harvested from naive C57Bl/6 donor mice treated by daily oral administration of L. casei or NaCl as control for 14 days, were co-transferred with CD8+ T cells from naive C57Bl/6 into syngenic CD3ε°/° recipients one day before skin sensitization and the CHS response to DNFB was examined after ear challenge with DNFB (Fig 6A). As described above (Fig 4B), CD3ε°/° recipient mice mounted a CHS response to DNFB only upon CD8 reconstitution, with a mean ear swelling of 330 µm±85 at day 4 after challenge, that was sustained for up to day 9 (Fig 6B). Co-transfer of Tregs cells from either NaCl- or L. casei- treated donors resulted in a similar 30% (p = 0.0076) reduction of skin inflammation with mean ear swelling values at 96 hr post challenge of 220 µm±92 and 230 µm±57, respectively. These data demonstrate that daily oral exposure to L. casei in a naive host is not capable to affect the potential of natural CD4+ CD25+ Treg of lymphoid organs to suppress a CHS response.

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