Chronic hypoxia reprograms human immature dendritic cells by inducing a proinflammatory phenotype and TREM-1 expression

Daniele Pierobon, Maria Carla Bosco, Fabiola Blengio, Federica Raggi, Alessandra Eva, Miriam Filippi, Tiziana Musso, Francesco Novelli, Paola Cappello, Luigi Varesio, Mirella Giovarelli

Research output: Contribution to journalArticle

Abstract

DCs are powerful antigen-presenting cells central in the orchestration of innate and acquired immunity. DC development, migration, and activities are intrinsically linked to the microenvironment. DCs migrate through pathologic tissues before reaching their final destination in the lymph nodes. Hypoxia, a condition of low partial oxygen pressure, is a common feature of many pathologic situations, capable of modifying DC phenotype and functional behavior. We studied human monocyte-derived immature DCs generated under chronic hypoxic conditions (H-iDCs). We demonstrate by gene expression profiling the upregulation of a cluster of genes coding for antigen-presentation, immunoregulatory, and pattern recognition receptors, suggesting a stimulatory role for hypoxia on iDC immunoregulatory functions. In particular, we show that H-iDCs express triggering receptor expressed on myeloid cells(TREM-1), a member of the Ig superfamily of immunoreceptors and an amplifier of inflammation. This effect is reversible because H-iDC reoxygenation results in TREM-1 down-modulation. TREM-1 engagement promotes upregulation of T-cell costimulatory molecules and homing chemokine receptors, typical of mature DCs, and increases the production of proinflammatory, Th1/Th17-priming cytokines/chemokines, resulting in increased T-cell responses. These results suggest that TREM-1 induction by the hypoxic microenvironment represents a mechanism of regulation of Th1-cell trafficking and activation by iDCs differentiated at pathologic sites.

Original languageEnglish
Pages (from-to)949-966
Number of pages18
JournalEuropean Journal of Immunology
Volume43
Issue number4
DOIs
Publication statusPublished - Apr 2013

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Dendritic Cells
Up-Regulation
T-Lymphocytes
Phenotype
Pattern Recognition Receptors
Th1 Cells
Partial Pressure
Chemokine Receptors
Antigen Presentation
Gene Expression Profiling
Adaptive Immunity
Antigen-Presenting Cells
Myeloid Cells
Multigene Family
Chemokines
Innate Immunity
Monocytes
Lymph Nodes
Cytokines
Oxygen

Keywords

  • Dendritic cells
  • Hypoxia
  • Immunoregulatory receptors
  • Innate immunity
  • Proinflammatory cytokines/chemokines

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Chronic hypoxia reprograms human immature dendritic cells by inducing a proinflammatory phenotype and TREM-1 expression. / Pierobon, Daniele; Bosco, Maria Carla; Blengio, Fabiola; Raggi, Federica; Eva, Alessandra; Filippi, Miriam; Musso, Tiziana; Novelli, Francesco; Cappello, Paola; Varesio, Luigi; Giovarelli, Mirella.

In: European Journal of Immunology, Vol. 43, No. 4, 04.2013, p. 949-966.

Research output: Contribution to journalArticle

Pierobon, Daniele ; Bosco, Maria Carla ; Blengio, Fabiola ; Raggi, Federica ; Eva, Alessandra ; Filippi, Miriam ; Musso, Tiziana ; Novelli, Francesco ; Cappello, Paola ; Varesio, Luigi ; Giovarelli, Mirella. / Chronic hypoxia reprograms human immature dendritic cells by inducing a proinflammatory phenotype and TREM-1 expression. In: European Journal of Immunology. 2013 ; Vol. 43, No. 4. pp. 949-966.
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