Differential expression of constitutive and inducible proteasome subunits in human monocyte-derived DC differentiated in the presence of IFN-α or IL-4

Valeria Tosello, Rita Zamarchi, Anna Merlo, Margherita Gorza, Erich Piovan, Susanna Mandruzzato, Vincenzo Bronte, Xinhui Wang, Soldano Ferrone, Alberto Amadori, Paola Zanovello

Research output: Contribution to journalArticle

Abstract

Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL-4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag-processing machinery (APM) profile in human DC grown in the presence of IFN-α (IFNDC) or IL-4 (IL-4DC). Using a panel of APM component-specific mAb in Western blot experiments, we found that IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature IL-4DC co-express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than IL-4DC. The different proteasome profiles of IFNDC and IL-4DC were associated with a greater ability of IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag-processing ability of DC.

Original languageEnglish
Pages (from-to)56-66
Number of pages11
JournalEuropean Journal of Immunology
Volume39
Issue number1
DOIs
Publication statusPublished - 2009

Fingerprint

Proteasome Endopeptidase Complex
Interleukin-4
Monocytes
Western Blotting
Calnexin
Calreticulin
Immunodominant Epitopes
Cytokines
In Vitro Techniques
LMP-2 protein
tapasin

Keywords

  • Antibodies
  • Antigen processing
  • Cytokines
  • Human DC

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

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title = "Differential expression of constitutive and inducible proteasome subunits in human monocyte-derived DC differentiated in the presence of IFN-α or IL-4",
abstract = "Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL-4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag-processing machinery (APM) profile in human DC grown in the presence of IFN-α (IFNDC) or IL-4 (IL-4DC). Using a panel of APM component-specific mAb in Western blot experiments, we found that IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature IL-4DC co-express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than IL-4DC. The different proteasome profiles of IFNDC and IL-4DC were associated with a greater ability of IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag-processing ability of DC.",
keywords = "Antibodies, Antigen processing, Cytokines, Human DC",
author = "Valeria Tosello and Rita Zamarchi and Anna Merlo and Margherita Gorza and Erich Piovan and Susanna Mandruzzato and Vincenzo Bronte and Xinhui Wang and Soldano Ferrone and Alberto Amadori and Paola Zanovello",
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T1 - Differential expression of constitutive and inducible proteasome subunits in human monocyte-derived DC differentiated in the presence of IFN-α or IL-4

AU - Tosello, Valeria

AU - Zamarchi, Rita

AU - Merlo, Anna

AU - Gorza, Margherita

AU - Piovan, Erich

AU - Mandruzzato, Susanna

AU - Bronte, Vincenzo

AU - Wang, Xinhui

AU - Ferrone, Soldano

AU - Amadori, Alberto

AU - Zanovello, Paola

PY - 2009

Y1 - 2009

N2 - Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL-4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag-processing machinery (APM) profile in human DC grown in the presence of IFN-α (IFNDC) or IL-4 (IL-4DC). Using a panel of APM component-specific mAb in Western blot experiments, we found that IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature IL-4DC co-express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than IL-4DC. The different proteasome profiles of IFNDC and IL-4DC were associated with a greater ability of IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag-processing ability of DC.

AB - Several studies strongly suggest that DC differentiated in vitro in the presence of type I IFN acquire more potent immune stimulatory properties, compared with DC differentiated in vitro with IL-4. However, little is known about the molecular mechanisms underlying this phenomenon. To address this question, we compared the Ag-processing machinery (APM) profile in human DC grown in the presence of IFN-α (IFNDC) or IL-4 (IL-4DC). Using a panel of APM component-specific mAb in Western blot experiments, we found that IFNDC preferentially express inducible proteasome subunits (LMP2, LMP7, and MECL1) both at immature and mature stages. In contrast, immature IL-4DC co-express both constitutive (β1, β2, and β5) and inducible subunits, as shown by Western blotting analysis. In addition, immature IFNDC express higher levels of TAP1, TAP2, calnexin, calreticulin, tapasin, and HLA class I molecules than IL-4DC. The different proteasome profiles of IFNDC and IL-4DC were associated with a greater ability of IFNDC to present an immunodominant epitope that requires LMP7 expression for its processing. In general, these data show the impact of cytokines on APM component expression and hence the Ag-processing ability of DC.

KW - Antibodies

KW - Antigen processing

KW - Cytokines

KW - Human DC

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