title: Constraints for monocyte-derived dendritic cell functions under inflammatory conditions.
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.
authors: Department of Immunology, University of Debrecen, Debrecen, Hungary.
authors: Tünde
authors: T
authors: Fekete
authors: Attila
authors: A
authors: Szabo
authors: Luca
authors: L
authors: Beltrame
authors: Nancy
authors: N
authors: Vivar
authors: Andor
authors: A
authors: Pivarcsi
authors: Arpad
authors: A
authors: Lanyi
authors: Duccio
authors: D
authors: Cavalieri
authors: Eva
authors: E
authors: Rajnavölgyi
authors: Bence
authors: B
authors: Rethi
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D011956:Receptors, Cell Surface; C000604059:SLAMF1 protein, human; C108944:SOCS1 protein, human; D050796:STAT3 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D051193:Toll-Like Receptors; D016753:Interleukin-10; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D053592:Interleukin-1 Receptor-Associated Kinases