Leukocyte signaling

Constraints for monocyte-derived dendritic cell functions under inflammatory conditions

  1. Tünde Fekete1,†,
  2. Attila Szabo1,†,
  3. Luca Beltrame2,
  4. Nancy Vivar3,
  5. Andor Pivarcsi4,
  6. Arpad Lanyi1,
  7. Duccio Cavalieri2,
  8. Eva Rajnavölgyi1,*,
  9. Bence Rethi3,*

Article first published online: 14 DEC 2011

DOI: 10.1002/eji.201141924

Issue

European Journal of Immunology

European Journal of Immunology

Volume 42, Issue 2, pages 458–469, February 2012

Additional Information

How to Cite

Fekete, T., Szabo, A., Beltrame, L., Vivar, N., Pivarcsi, A., Lanyi, A., Cavalieri, D., Rajnavölgyi, E. and Rethi, B. (2012), Constraints for monocyte-derived dendritic cell functions under inflammatory conditions. Eur. J. Immunol., 42: 458–469. doi: 10.1002/eji.201141924

Author Information

  1. 1

    Department of Immunology, University of Debrecen, Debrecen, Hungary

  2. 2

    Department of Pharmacology, University of Firenze, Firenze, Italy

  3. 3

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden

  4. 4

    Molecular Dermatology Research Group, Unit of Dermatology and Venerology, Department of Medicine, Karolinska Institute, Stockholm, Sweden

  1. †

    These authors contributed equally to this work.

*Department of Immunology, University of Debrecen, Egyetem ter1, Debrecen 4032, Hungary Fax: +3652417159

Publication History

  1. Issue published online: 20 JAN 2012
  2. Article first published online: 14 DEC 2011
  3. Accepted manuscript online: 7 NOV 2011 02:30AM EST
  4. Manuscript Accepted: 26 OCT 2011
  5. Manuscript Revised: 30 SEP 2011
  6. Manuscript Received: 6 JUL 2011

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Keywords:

  • DC;
  • Endotoxin tolerance;
  • IRAK-1;
  • TLR

Abstract

The activation of TLRs expressed by macrophages or DCs, in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known, however, which of these can lead to long-lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte-derived DCs (MoDCs) is influenced in inflamed tissues by the continuous presence of stimulatory signals during their differentiation. Here we studied the role of a wide range of DC-inhibitory mechanisms in a simple and robust model of MoDC inactivation induced by early TLR signals during differentiation. We show that the activation-induced suppressor of cytokine signaling 1 (SOCS1), IL-10, STAT3, miR146a and CD150 (SLAM) molecules possessed short-term inhibitory effects on cytokine production but did not induce persistent DC inactivation. On the contrary, the LPS-induced IRAK-1 downregulation could alone lead to persistent MoDC inactivation. Studying cellular functions in line with the activation-induced negative feedback mechanisms, we show that early activation of developing MoDCs allowed only a transient cytokine production that was followed by the downregulation of effector functions and the preservation of a tissue-resident non-migratory phenotype.

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