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  • Fekete, Tünde, et al. (author)
  • Constraints for monocyte-derived dendritic cell functions under inflammatory conditions.
  • 2012
  • In: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 42:2, s. 458-69
  • Journal article (peer-reviewed)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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Type of publication
journal article (1)
Type of content
peer-reviewed (1)
Author/Editor
Pivarcsi, Andor (1)
Szabó, Attila (1)
Rethi, Bence (1)
Vivar, Nancy (1)
Fekete, Tünde (1)
Beltrame, Luca (1)
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Lanyi, Arpad (1)
Cavalieri, Duccio (1)
Rajnavölgyi, Eva (1)
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University
Uppsala University (1)
Karolinska Institutet (1)
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English (1)
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Medical and Health Sciences (1)
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