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Hypoxia: a double-edged sword of immunity

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Abstract

Hypoxia is a condition of low oxygen tension that characterizes virtually every site of inflammation, tissue damage, and neoplasia. Hypoxic environment attracts infiltrating immune cells that move against oxygen gradients and respond to these demanding conditions by switching to anaerobic metabolism to maintain their energy requirements. Several lines of evidence suggest that oxygen deprivation causes opposite effects on the innate or adaptive immune responses. We will review the evidence that the hypoxic environment promotes the recruitment, activation, and survival of innate immune cells while inhibiting the adaptive immunity through downregulation of effector lymphocyte functions. This divergent regulation of the innate and adaptive immunity appears to reflect evolutionary mechanisms aimed to both guarantee tissue homeostasis and provide safeguard mechanisms against autoimmunity. Selective inhibition of hypoxic signaling pathways in myeloid versus lymphoid cells may open new therapeutic opportunities in diseases characterized by low oxygen tension.

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Acknowledgments

This work was supported by Associazione Italiana Ricerca sul Cancro (AIRC), Italy; Fondazione Berlucchi, Italy; European Commission (project Mugen); Ministero Università Ricerca (MUR), Italy; Associazione Italiana Glicogenosi; Fondazione Italiana per la lotta al neuroblastoma; and Ministero della Salute and by Regione Piemonte (project number 331, August 8th, 2009).

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Authors and Affiliations

  1. Istituto Clinico Humanitas, IRCCS, Italy via Manzoni, 56, 20089, Rozzano, Milan, Italy

    Antonio Sica

  2. DISCAFF, University of Piemonte, Orientale A. Avogadro, 28100, Novara, Italy

    Antonio Sica

  3. Developmental Therapeutics Program, SAIC Frederick, Inc., NCI at Frederick, Frederick, MD, USA

    Giovanni Melillo

  4. Laboratory of Molecular Biology, G. Gaslini Institute, Genova, Italy

    Luigi Varesio

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  1. Antonio Sica
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  2. Giovanni Melillo
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  3. Luigi Varesio
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Correspondence to Antonio Sica.

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Sica, A., Melillo, G. & Varesio, L. Hypoxia: a double-edged sword of immunity. J Mol Med 89, 657–665 (2011). https://doi.org/10.1007/s00109-011-0724-8

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