A newly established murine immature dendritic cell line can be differentiated into a mature state, but exerts tolerogenic function upon maturation in the presence of glucocorticoid.
The phenotype and function of murine dendritic cells (DCs) are primarily studied using bone-marrow-derived DCs (BM-DCs), but may be hampered by the heterogeneous phenotype of BM-DCs due to their differential state of maturation. Here we characterize a newly established murine DC line (SP37A3) of myeloid origin. During maintainance in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and M-CSF, SP37A3 cells resemble immature DCs characterized by low expression of major histocompatibility complex (MHC) II and costimulatory molecules and low T-cell stimulatory capacity. Upon stimulation, SP37A3 cells acquire a mature phenotype and activate naive T cells as potently as BM-DCs. Similar to BM-DCs, SP37A3 cells activated in the presence of dexamethasone-induced regulatory T cells, which were anergic upon restimulation and suppressed proliferation of naive T cells. This tolerogenic state was reflected by lower expression levels of costimulatory molecules and proinflammatory cytokines compared with mature cells, as well as up-regulated expression of FcgammaRIIB and interleukin-1RA (IL-1RA). SP37A3 cells were responsive to dexamethasone even when applied at later time points during activation, suggesting functional plasticity. Thus, DC line SP37A3 represents a suitable model to study functions of immature and mature as well as tolerogenic myeloid DCs, circumventing restrictions associated with the use of primary DCs and BM-DCs.
Bros
Matthias
M
Clinical Research Unit Allergology, Department of Dermatology, Johannes Gutenberg-University, Obere Zahlbacher Strasse 63, D-55131 Mainz, Germany.
Jährling
Frank
F
Renzing
Andrea
A
Wiechmann
Nadine
N
Dang
Ngoc-Anh
NA
Sutter
Arne
A
Ross
Ralf
R
Knop
Jürgen
J
Sudowe
Stephan
S
Reske-Kunz
Angelika B
AB
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D017635:Clonal Anergy / Q000187:drug effects* / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D023461:Myeloid Progenitor Cells / Q000166:cytology / Q000276:immunology; D017452:Receptors, IgG / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D016207:Cytokines; C499172:Fcgr2b protein, mouse; D005938:Glucocorticoids; D000949:Histocompatibility Antigens Class II; D053590:Interleukin 1 Receptor Antagonist Protein; D017452:Receptors, IgG; D003907:Dexamethasone