Dendritic cells (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 condition (H-iDCs). We demonstrate, by gene expression profiling, the up-regulation of a cluster of genes coding for antigen-presentation, immunoregulatory, and pattern recognition receptors, suggesting a stimulatory role for hypoxia on iDCs immunoregulatory functions. In particular, we show that H-iDCs express TREM-1, a member of the Ig superfamily of immunoreceptors and an amplifier of inflammation. This effect is reversible because H-iDCs reoxygenation results in TREM-1 down-modulation. TREM-1 engagement promotes up-regulation 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.

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

PIEROBON, DANIELE;MUSSO, Tiziana;NOVELLI, Francesco;CAPPELLO, Paola;GIOVARELLI, Mirella
2013

Abstract

Dendritic cells (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 condition (H-iDCs). We demonstrate, by gene expression profiling, the up-regulation of a cluster of genes coding for antigen-presentation, immunoregulatory, and pattern recognition receptors, suggesting a stimulatory role for hypoxia on iDCs immunoregulatory functions. In particular, we show that H-iDCs express TREM-1, a member of the Ig superfamily of immunoreceptors and an amplifier of inflammation. This effect is reversible because H-iDCs reoxygenation results in TREM-1 down-modulation. TREM-1 engagement promotes up-regulation 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.
Il contributo della patologia generale alla medicina traslazionale
Torino
1,2 Febbraio 2013
Scuola M. U. Dianzani Riunione Scientifica 2012-2013
Dipartimento di Scienze Cliniche e Biologiche
1
14
14
dendritic cells; Hypoxia; TREM-1
D. Pierobon, MC Bosco , F. Blengio, F. Raggi, A Eva,M. Filippi, T. Musso;F. Novelli, P. Cappello, L. Varesio, M. Giovarelli
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/141393
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