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001-es BibID:	BIBFORM032051
Első szerző:	Fekete Tünde (immunológus, molekuláris biológus, mikrobiológus)
Cím:	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
Dátum:	2012
ISSN:	0014-2980
Megjegyzések:	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.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban DC Endotoxin tolerance IRAK-1 TLR
Megjelenés:	European Journal of Immunology 42 : 2 (2012), p. 458-469. -
További szerzők:	Szabó Attila (1981-) (molekuláris biológus, immunológus, filozófus) Beltrame, Luca Vivar, Nancy Pivarcsi Andor Lányi Árpád (1962-) (biológus, immunológus) Cavalieri, Duccio Rajnavölgyi Éva (1950-) (immunológus) Réthi Bence (1973-) (biológus, immunológus)
Pályázati támogatás:	TORNADO 222720 (felhívás kód: FP7-KBBE-2007-2A) FP7
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM049591
Első szerző:	Nasi, Aikaterini
Cím:	Dendritic cell reprogramming by endogenously produced lactic acid / Aikaterini Nasi, Tünde Fekete, Akilan Krishnamurthy, Stuart Snowden, Eva Rajnavölgyi, Anca I. Catrina, Craig E. Wheelock, Nancy Vivar, Bence Rethi
Dátum:	2013
ISSN:	0022-1767 1550-6606
Megjegyzések:	The demand for controlling T cell responses via dendritic cell (DC) vaccines initiated a quest for reliable and feasible DC modulatory strategies that would facilitate cytotoxicity against tumors or tolerance in autoimmunity. We studied endogenous mechanisms in developing monocyte-derived DCs (MoDCs) that can induce inflammatory or suppressor programs during differentiation, and we identified a powerful autocrine pathway that, in a cell concentration-dependent manner, strongly interferes with inflammatory DC differentiation. MoDCs developing at low cell culture density have superior ability to produce inflammatory cytokines, to induce Th1 polarization, and to migrate toward the lymphoid tissue chemokine CCL19. On the contrary, MoDCs originated from dense cultures produce IL-10 but no inflammatory cytokines upon activation. DCs from high-density cultures maintained more differentiation plasticity and can develop to osteoclasts. The cell concentration-dependent pathway was independent of peroxisome proliferator-activated receptor gamma (PPAR gamma), a known endogenous regulator of MoDC differentiation. Instead, it acted through lactic acid, which accumulated in dense cultures and induced an early and long-lasting reprogramming of MoDC differentiation. Our results suggest that the lactic acid-mediated inhibitory pathway could be efficiently manipulated in developing MoDCs to influence the immunogenicity of DC vaccines.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban myeloid suppressor-cells par-gamma cancer-immunotherapy differentitation activation expression environment metabolism carcinoma migration Doktori iskola
Megjelenés:	Journal of Immunology. - 191 : 6 (2013), p. 3090-3099. -
További szerzők:	Fekete Tünde (1984-) (immunológus, molekuláris biológus, mikrobiológus) Krishnamurthy, Akilan Snowden, Stuart Rajnavölgyi Éva (1950-) (immunológus) Catrina, Anca I. Wheelock, Craig E. Vivar, Nancy Réthi Bence (1973-) (biológus, immunológus)
Pályázati támogatás:	TÁMOP-4.2.2/B-10/1-2010-0024 TÁMOP Molekuláris Sejt- és Immunbiológiai Doktori Iskola
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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