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001-es BibID:BIBFORM068268
035-os BibID:(cikkazonosító)427 (WoS)000399425000003 (Scopus)85018375753
Első szerző:Bene Krisztián (Biológus)
Cím:Gut Microbiota Species Can Provoke both Inflammatory and Tolerogenic Immune Responses in Human Dendritic Cells Mediated by Retinoic Acid Receptor Alpha Ligation / Krisztian Bene, Zsofia Varga, Viktor O. Petrov, Nadiya Boyko, Eva Rajnavolgyi
Dátum:2017
Megjegyzések:Dendritic cells are considered as the main coordinators of both mucosal and systemic immune responses, thus playing a determining role in shaping the outcome of effector cell responses. However, it is still uncovered how primary human monocyte-derived DC (moDC) populations drive the polarization of helper T (Th) cells in the presence of commensal bacteria harboring unique immunomodulatory properties. Furthermore,the individual members of the gut microbiota have the potential to modulate the outcomeof immune responses and shape the immunogenicity of differentiating moDCsvia the activation of retinoic acid receptor alpha (RAR?). Here, we report that moDCs are able to mediate robust Th1 and Th17 responses upon stimulation by Escherichiacoli Schaedler or Morganella morganii, while the probiotic Bacillus subtilis strain limits this effect. Moreover, physiological concentrations of all-trans retinoic acid (ATRA) are able to re-program the differentiation of moDCs resulting in altered gene expression profiles of the master transcription factors RAR? and interferon regulatory factor 4, andconcomitantly regulate the cell surface expression levels of CD1 proteins and also the mucosa-associated CD103 integrin to different directions. It was also demonstrated that the ATRA-conditioned moDCs exhibited enhanced pro-inflammatory cytokine secretion while reduced their co-stimulatory and antigen-presenting capacity thus reducing Th1 and presenting undetectable Th17 type responses against the tested microbiota strains.Importantly, these regulatory circuits could be prevented by the selective inhibition of RAR? functionality. These results altogether demonstrate that selected commensal bacterialstrains are able to drive strong effector immune responses by moDCs, while in the presence of ATRA, they support the development of both tolerogenic and inflammatory moDC in a RAR?-dependent manner.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
immunológia
mikrobiológia
dendritikus sejt
mikrobióta
A-vitamin
retinsav
T sejt
Megjelenés:Frontiers in Immunology. - 8 : 427 (2017), p. 1-17. -
További szerzők:Varga Zsófia (1992-) (molekuláris biológus) Petrov, Viktor O. Boyko, Nadiya V. Rajnavölgyi Éva (1950-) (immunológus)
Pályázati támogatás:TAMOP 4.2.4.A/2-11-1- 2012-0001
TÁMOP
TAMOP 4.2.2.A-11/1/KONV-2012-0023
TÁMOP
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