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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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CD8+ T cells from L. casei-treated mice generate a weak CHS in CD3ε°/° recipients.(A) Naïve C57Bl/6 were treated daily for 2 weeks with either L. casei or NaCl 0.9%. On Day -1, pooled CD8+ T cells (10.106) from pLN, mLN and spleens from each group of mice were transferred i.v. to naive CD3ε°/° recipient mice. On day 0 all CD3ε°/° recipients were DNFB sensitized and ear challenged with DNFB on Day 5. (B) Ear swelling at 48 h after DNFB-challenge was determined in CD3ε°/° recipients transferred with CD8+ T cells from either L. casei-treated (black circle) or NaCl-treated (white circle) C57Bl/6 donors as well as in untransferred control CD3ε°/° mice (white losange).
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pone-0004903-g004: CD8+ T cells from L. casei-treated mice generate a weak CHS in CD3ε°/° recipients.(A) Naïve C57Bl/6 were treated daily for 2 weeks with either L. casei or NaCl 0.9%. On Day -1, pooled CD8+ T cells (10.106) from pLN, mLN and spleens from each group of mice were transferred i.v. to naive CD3ε°/° recipient mice. On day 0 all CD3ε°/° recipients were DNFB sensitized and ear challenged with DNFB on Day 5. (B) Ear swelling at 48 h after DNFB-challenge was determined in CD3ε°/° recipients transferred with CD8+ T cells from either L. casei-treated (black circle) or NaCl-treated (white circle) C57Bl/6 donors as well as in untransferred control CD3ε°/° mice (white losange).

Mentions: We recently reported that orally-induced tolerance of CD8+ T cell-mediated CHS to DNFB is initiated by a mucosal step of in vivo CD8+ T cell hyporesponsiveness, which impairs further differentiation of CD8+ T cells into CHS effectors [25]. To determine whether oral administration of L. casei could induce a similar conditioning of naive CD8+ T cells in lymphoid organs, we set up a model of CHS induced by adoptive transfer of CD8+ T cells into T cell deficient CD3ε°/° mice. MACS-sorted CD8+ T cells from naive C57Bl/6 donor mice that were treated daily for 14 days by oral administration of L. casei or NaCl, were transferred i.v. into naive syngenic CD3ε°/° recipients and the CHS response to DNFB was examined in the recipients (Fig 4A). As expected, un-reconstituted CD3ε°/° recipient mice were unable to mount a CHS response while reconstitution with CD8+ T cells from control NaCl treated donors induced a potent CHS response (mean ear swelling 237 µm±71). In contrast, skin inflammation in recipients of CD8+ T cells from L. casei treated donors, was significantly reduced (mean ear swelling 173.8 µm±18, Fig 4B). Thus, naive CD8+ T cells from systemic lymphoid organs conditioned by oral L casei in vivo, exhibited impaired ability to induce a CHS response in vivo.


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)

CD8+ T cells from L. casei-treated mice generate a weak CHS in CD3ε°/° recipients.(A) Naïve C57Bl/6 were treated daily for 2 weeks with either L. casei or NaCl 0.9%. On Day -1, pooled CD8+ T cells (10.106) from pLN, mLN and spleens from each group of mice were transferred i.v. to naive CD3ε°/° recipient mice. On day 0 all CD3ε°/° recipients were DNFB sensitized and ear challenged with DNFB on Day 5. (B) Ear swelling at 48 h after DNFB-challenge was determined in CD3ε°/° recipients transferred with CD8+ T cells from either L. casei-treated (black circle) or NaCl-treated (white circle) C57Bl/6 donors as well as in untransferred control CD3ε°/° mice (white losange).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654141&req=5

pone-0004903-g004: CD8+ T cells from L. casei-treated mice generate a weak CHS in CD3ε°/° recipients.(A) Naïve C57Bl/6 were treated daily for 2 weeks with either L. casei or NaCl 0.9%. On Day -1, pooled CD8+ T cells (10.106) from pLN, mLN and spleens from each group of mice were transferred i.v. to naive CD3ε°/° recipient mice. On day 0 all CD3ε°/° recipients were DNFB sensitized and ear challenged with DNFB on Day 5. (B) Ear swelling at 48 h after DNFB-challenge was determined in CD3ε°/° recipients transferred with CD8+ T cells from either L. casei-treated (black circle) or NaCl-treated (white circle) C57Bl/6 donors as well as in untransferred control CD3ε°/° mice (white losange).
Mentions: We recently reported that orally-induced tolerance of CD8+ T cell-mediated CHS to DNFB is initiated by a mucosal step of in vivo CD8+ T cell hyporesponsiveness, which impairs further differentiation of CD8+ T cells into CHS effectors [25]. To determine whether oral administration of L. casei could induce a similar conditioning of naive CD8+ T cells in lymphoid organs, we set up a model of CHS induced by adoptive transfer of CD8+ T cells into T cell deficient CD3ε°/° mice. MACS-sorted CD8+ T cells from naive C57Bl/6 donor mice that were treated daily for 14 days by oral administration of L. casei or NaCl, were transferred i.v. into naive syngenic CD3ε°/° recipients and the CHS response to DNFB was examined in the recipients (Fig 4A). As expected, un-reconstituted CD3ε°/° recipient mice were unable to mount a CHS response while reconstitution with CD8+ T cells from control NaCl treated donors induced a potent CHS response (mean ear swelling 237 µm±71). In contrast, skin inflammation in recipients of CD8+ T cells from L. casei treated donors, was significantly reduced (mean ear swelling 173.8 µm±18, Fig 4B). Thus, naive CD8+ T cells from systemic lymphoid organs conditioned by oral L casei in vivo, exhibited impaired ability to induce a CHS response in vivo.

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