title: PPARγ modulated inflammatory response of human dendritic cell subsets to engulfed apoptotic neutrophils.
abstract: The means of how phagocytes handle apoptotic cells has a great impact on the outcome of immune responses. Here, we show that phagocytosis of allogeneic, apoptotic neutrophils by human monocyte-derived DCs is slow and less efficient than that of macrophages, and CD1a(-) DCs are more active in the engulfment of apoptotic neutrophils than CD1a(+) DCs. Blocking DC-SIGN function partially interferes with the uptake of apoptotic cells, and long-term interaction of apoptotic neutrophils with DCs makes them prone to proinflammatory cytokine responses. Engulfment of apoptotic cells sensitizes CD1a(-) DCs for high IL-8, TNF-α, IL-6, and CD1a(+) cells for IL-12 and IL-10 cytokine secretion elicited by additional inflammatory stimuli, which also result in the polarization of autologous T lymphocytes to Th1 effector cells. Ligand-induced activation of PPARγ by RSG results in enhanced phagocytosis, but the proinflammatory response and the capacity to trigger Th1 cell activation of CD1a(-) DCs are not enhanced. These results demonstrate that DCs are able to respond to allogeneic, apoptotic neutrophils with inflammatory cytokines and T cell responses in a subtype-specific manner that is modulated by the anti-inflammatory effects of PPARγ.
authors.affiliation: Research Center for Molecular Medicine, University of Debrecen, Egyetem tér 1, Debrecen, Hungary.
authors.forename: Gyöngyike
authors.initials: G
authors.lastname: Majai
authors.forename: Péter
authors.initials: P
authors.lastname: Gogolák
authors.forename: Csilla
authors.initials: C
authors.lastname: Ambrus
authors.forename: György
authors.initials: G
authors.lastname: Vereb
authors.forename: Judit
authors.initials: J
authors.lastname: Hodrea
authors.forename: László
authors.initials: L
authors.lastname: Fésüs
authors.forename: Eva
authors.initials: E
authors.lastname: Rajnavölgyi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000911:Antibodies, Monoclonal; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000502:physiology; D018613:Microscopy, Confocal; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D047495:PPAR gamma / Q000494:pharmacology*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology; D047488:Retinoid X Receptors / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016207:Cytokines; D015850:Interleukin-6; D047495:PPAR gamma; D047488:Retinoid X Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma