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.
| Original language | English |
|---|---|
| Pages (from-to) | 458-469 |
| Number of pages | 12 |
| Journal | European Journal of Immunology |
| Volume | 42 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2012 |
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Keywords
- DC
- Endotoxin tolerance
- IRAK-1
- TLR
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Constraints for monocyte-derived dendritic cell functions under inflammatory conditions. / Fekete, Tünde; Szabo, Attila; Beltrame, Luca; Vivar, Nancy; Pivarcsi, Andor; Lanyi, Arpad; Cavalieri, Duccio; Rajnavölgyi, Eva; Rethi, Bence.
In: European Journal of Immunology, Vol. 42, No. 2, 02.2012, p. 458-469.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Constraints for monocyte-derived dendritic cell functions under inflammatory conditions
AU - Fekete, Tünde
AU - Szabo, Attila
AU - Beltrame, Luca
AU - Vivar, Nancy
AU - Pivarcsi, Andor
AU - Lanyi, Arpad
AU - Cavalieri, Duccio
AU - Rajnavölgyi, Eva
AU - Rethi, Bence
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - DC
KW - Endotoxin tolerance
KW - IRAK-1
KW - TLR
UR - http://www.scopus.com/inward/record.url?scp=84856032655&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84856032655&partnerID=8YFLogxK
U2 - 10.1002/eji.201141924
DO - 10.1002/eji.201141924
M3 - Article
C2 - 22057588
AN - SCOPUS:84856032655
VL - 42
SP - 458
EP - 469
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 2
ER -