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CX₃CL1 (fractalkine) and its receptor CX₃CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin.

Staumont-Sallé D, Fleury S, Lazzari A, Molendi-Coste O, Hornez N, Lavogiez C, Kanda A, Wartelle J, Fries A, Pennino D, Mionnet C, Prawitt J, Bouchaert E, Delaporte E, Glaichenhaus N, Staels B, Julia V, Dombrowicz D - J. Exp. Med. (2014)

Bottom Line: CX3CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX3CR1 expression by both Th2 and Th1 cells was required to induce AD.Surprisingly, unlike in allergic asthma, where CX3CL1 and CX3CR1 regulate the pathology by controlling effector CD4(+) T cell survival within inflamed tissues, adoptive transfer experiments established CX3CR1 as a key regulator of CD4(+) T cell retention in inflamed skin, indicating a new function for this chemokine receptor.Therefore, although CX3CR1 and CX3CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases.

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Affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France Department of Dermatology, Claude-Huriez Hospital, 59037 Lille, France.

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CX3CR1 is expressed by skin-infiltrating CD4+ T cells in AD patients. (A) CX3CR1 expression by circulating CD4+ T cells. PBMCs from patients with AD or from healthy donors were analyzed by flow cytometry for CX3CR1 expression. Data show frequency of CX3CR1+ cells among CD4+ T cells in individual donors. (B) Cells from skin biopsies were characterized by surface and intracellular staining by flow cytometry. Left panel shows a representative FACS profile. Numbers indicate the mean ± SEM of the frequency of CX3CR1+ among CD4+ T cells from n = 6 patients. Right panels show frequencies of cytokine-secreting CX3CR1+ and CX3CR1− CD4+ T cells for each patient. Error bars indicate SEM.
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fig6: CX3CR1 is expressed by skin-infiltrating CD4+ T cells in AD patients. (A) CX3CR1 expression by circulating CD4+ T cells. PBMCs from patients with AD or from healthy donors were analyzed by flow cytometry for CX3CR1 expression. Data show frequency of CX3CR1+ cells among CD4+ T cells in individual donors. (B) Cells from skin biopsies were characterized by surface and intracellular staining by flow cytometry. Left panel shows a representative FACS profile. Numbers indicate the mean ± SEM of the frequency of CX3CR1+ among CD4+ T cells from n = 6 patients. Right panels show frequencies of cytokine-secreting CX3CR1+ and CX3CR1− CD4+ T cells for each patient. Error bars indicate SEM.

Mentions: To assess the human relevance of our observations, we investigated whether CX3CR1+ CD4+ T cells could be detected in AD patients. In agreement with the absence of CX3CR1 expression on circulating mouse CD4+ T cells, even upon antigenic sensitization, in human, we detected a very low expression on circulating CD4+ T cells from AD patients. In addition, no significant differences were found between healthy individuals and AD and psoriasis patients in agreement with previously published work (Fig. 6 A; Echigo et al., 2004). About 7% of skin-isolated CD4+ T cells expressed CX3CR1, in keeping with our findings in the murine model of AD. As CX3CR1− cells, CX3CR1+ CD4+ T cells display a very heterogeneous cytokine profile, with the Th1 and Th2 subsets being the most represented as compared with Th17 (Fig. 6 B). Collectively, these data confirm the presence and functional properties of CX3CR1 cells in human.


CX₃CL1 (fractalkine) and its receptor CX₃CR1 regulate atopic dermatitis by controlling effector T cell retention in inflamed skin.

Staumont-Sallé D, Fleury S, Lazzari A, Molendi-Coste O, Hornez N, Lavogiez C, Kanda A, Wartelle J, Fries A, Pennino D, Mionnet C, Prawitt J, Bouchaert E, Delaporte E, Glaichenhaus N, Staels B, Julia V, Dombrowicz D - J. Exp. Med. (2014)

CX3CR1 is expressed by skin-infiltrating CD4+ T cells in AD patients. (A) CX3CR1 expression by circulating CD4+ T cells. PBMCs from patients with AD or from healthy donors were analyzed by flow cytometry for CX3CR1 expression. Data show frequency of CX3CR1+ cells among CD4+ T cells in individual donors. (B) Cells from skin biopsies were characterized by surface and intracellular staining by flow cytometry. Left panel shows a representative FACS profile. Numbers indicate the mean ± SEM of the frequency of CX3CR1+ among CD4+ T cells from n = 6 patients. Right panels show frequencies of cytokine-secreting CX3CR1+ and CX3CR1− CD4+ T cells for each patient. Error bars indicate SEM.
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4042636&req=5

fig6: CX3CR1 is expressed by skin-infiltrating CD4+ T cells in AD patients. (A) CX3CR1 expression by circulating CD4+ T cells. PBMCs from patients with AD or from healthy donors were analyzed by flow cytometry for CX3CR1 expression. Data show frequency of CX3CR1+ cells among CD4+ T cells in individual donors. (B) Cells from skin biopsies were characterized by surface and intracellular staining by flow cytometry. Left panel shows a representative FACS profile. Numbers indicate the mean ± SEM of the frequency of CX3CR1+ among CD4+ T cells from n = 6 patients. Right panels show frequencies of cytokine-secreting CX3CR1+ and CX3CR1− CD4+ T cells for each patient. Error bars indicate SEM.
Mentions: To assess the human relevance of our observations, we investigated whether CX3CR1+ CD4+ T cells could be detected in AD patients. In agreement with the absence of CX3CR1 expression on circulating mouse CD4+ T cells, even upon antigenic sensitization, in human, we detected a very low expression on circulating CD4+ T cells from AD patients. In addition, no significant differences were found between healthy individuals and AD and psoriasis patients in agreement with previously published work (Fig. 6 A; Echigo et al., 2004). About 7% of skin-isolated CD4+ T cells expressed CX3CR1, in keeping with our findings in the murine model of AD. As CX3CR1− cells, CX3CR1+ CD4+ T cells display a very heterogeneous cytokine profile, with the Th1 and Th2 subsets being the most represented as compared with Th17 (Fig. 6 B). Collectively, these data confirm the presence and functional properties of CX3CR1 cells in human.

Bottom Line: CX3CR1 deficiency affected neither antigen presentation nor T cell proliferation in vivo upon skin sensitization, but CX3CR1 expression by both Th2 and Th1 cells was required to induce AD.Surprisingly, unlike in allergic asthma, where CX3CL1 and CX3CR1 regulate the pathology by controlling effector CD4(+) T cell survival within inflamed tissues, adoptive transfer experiments established CX3CR1 as a key regulator of CD4(+) T cell retention in inflamed skin, indicating a new function for this chemokine receptor.Therefore, although CX3CR1 and CX3CL1 act through distinct mechanisms in different pathologies, our results further indicate their interest as promising therapeutic targets in allergic diseases.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, FranceInstitut National de la Santé et de la Recherche Médicale U1011, Institut Pasteur de Lille and Université Lille 2, 59019 Lille, France European Genomic Institute of Diabetes, 59045 Lille, France Department of Dermatology, Claude-Huriez Hospital, 59037 Lille, France.

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Related in: MedlinePlus