IL-10 Conditioning of Human Skin Affects the Distribution of Migratory Dendritic Cell Subsets and Functional T Cell Differentiation

Jelle J. Lindenberg, Dinja Oosterhoff, Claudia C. Sombroek, Sinéad M. Lougheed, Erik Hooijberg, Anita G M Stam, Saskia J A M Santegoets, Henk J. Tijssen, Jan Buter, Herbert M. Pinedo, Alfons J M van den Eertwegh, Rik J. Scheper, Hans J P M Koenen, Rieneke van de Ven, Tanja D. de Gruijl

Research output: Contribution to journalArticle

Abstract

In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC) and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14+CD141+DC-SIGN+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8+ T cells, migration of immature CD14+ DDC was accompanied by increased release of IL-10, poor expansion of CD4+ and CD8+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.

Original languageEnglish (US)
Article numbere70237
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 18 2013
Externally publishedYes

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T-cells
dendritic cells
interleukin-10
skin (animal)
cell differentiation
Interleukin-10
Dendritic Cells
Cell Differentiation
Skin
T-lymphocytes
T-Lymphocytes
immatures
Langerhans Cells
neoplasms
Tumors
explants
cytokines
Cytokines
Langerhans cells
Tumor Microenvironment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lindenberg, J. J., Oosterhoff, D., Sombroek, C. C., Lougheed, S. M., Hooijberg, E., Stam, A. G. M., ... de Gruijl, T. D. (2013). IL-10 Conditioning of Human Skin Affects the Distribution of Migratory Dendritic Cell Subsets and Functional T Cell Differentiation. PLoS One, 8(7), [e70237]. https://doi.org/10.1371/journal.pone.0070237

IL-10 Conditioning of Human Skin Affects the Distribution of Migratory Dendritic Cell Subsets and Functional T Cell Differentiation. / Lindenberg, Jelle J.; Oosterhoff, Dinja; Sombroek, Claudia C.; Lougheed, Sinéad M.; Hooijberg, Erik; Stam, Anita G M; Santegoets, Saskia J A M; Tijssen, Henk J.; Buter, Jan; Pinedo, Herbert M.; van den Eertwegh, Alfons J M; Scheper, Rik J.; Koenen, Hans J P M; van de Ven, Rieneke; de Gruijl, Tanja D.

In: PLoS One, Vol. 8, No. 7, e70237, 18.07.2013.

Research output: Contribution to journalArticle

Lindenberg, JJ, Oosterhoff, D, Sombroek, CC, Lougheed, SM, Hooijberg, E, Stam, AGM, Santegoets, SJAM, Tijssen, HJ, Buter, J, Pinedo, HM, van den Eertwegh, AJM, Scheper, RJ, Koenen, HJPM, van de Ven, R & de Gruijl, TD 2013, 'IL-10 Conditioning of Human Skin Affects the Distribution of Migratory Dendritic Cell Subsets and Functional T Cell Differentiation', PLoS One, vol. 8, no. 7, e70237. https://doi.org/10.1371/journal.pone.0070237
Lindenberg, Jelle J. ; Oosterhoff, Dinja ; Sombroek, Claudia C. ; Lougheed, Sinéad M. ; Hooijberg, Erik ; Stam, Anita G M ; Santegoets, Saskia J A M ; Tijssen, Henk J. ; Buter, Jan ; Pinedo, Herbert M. ; van den Eertwegh, Alfons J M ; Scheper, Rik J. ; Koenen, Hans J P M ; van de Ven, Rieneke ; de Gruijl, Tanja D. / IL-10 Conditioning of Human Skin Affects the Distribution of Migratory Dendritic Cell Subsets and Functional T Cell Differentiation. In: PLoS One. 2013 ; Vol. 8, No. 7.
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abstract = "In cancer patients pervasive systemic suppression of Dendritic Cell (DC) differentiation and maturation can hinder vaccination efficacy. In this study we have extensively characterized migratory DC subsets from human skin and studied how their migration and T cell-stimulatory abilities were affected by conditioning of the dermal microenvironment through cancer-related suppressive cytokines. To assess effects in the context of a complex tissue structure, we made use of a near-physiological skin explant model. By 4-color flow cytometry, we identified migrated Langerhans Cells (LC) and five dermis-derived DC populations in differential states of maturation. From a panel of known tumor-associated suppressive cytokines, IL-10 showed a unique ability to induce predominant migration of an immature CD14+CD141+DC-SIGN+ DC subset with low levels of co-stimulatory molecules, up-regulated expression of the co-inhibitory molecule PD-L1 and the M2-associated macrophage marker CD163. A similarly immature subset composition was observed for DC migrating from explants taken from skin overlying breast tumors. Whereas predominant migration of mature CD1a+ subsets was associated with release of IL-12p70, efficient Th cell expansion with a Th1 profile, and expansion of functional MART-1-specific CD8+ T cells, migration of immature CD14+ DDC was accompanied by increased release of IL-10, poor expansion of CD4+ and CD8+ T cells, and skewing of Th responses to favor coordinated FoxP3 and IL-10 expression and regulatory T cell differentiation and outgrowth. Thus, high levels of IL-10 impact the composition of skin-emigrated DC subsets and appear to favor migration of M2-like immature DC with functional qualities conducive to T cell tolerance.",
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