Cyclic adenosine monophosphate and IL-10 coordinately contribute to nTreg cell-mediated suppression of dendritic cell activation.
In humans and mice naturally occurring regulatory T cells (nTregs) are crucial for the maintenance of peripheral tolerance by controlling not only potentially autoreactive T cells but virtually all cells of the adaptive and innate immune system. Here we show that co-culture of murine dendritic cells (DC) and nTregs results in an immediate increase of cAMP in DC, responsible for a rapid down-regulation of co-stimulatory molecules (CD80, CD86). In addition, the inhibitory surface molecule B7-H3 on DC is up-regulated. Subsequently, nTreg-derived IL-10 inhibits the cytokine production (IL-6, IL-12) of suppressed DC therewith preserving their silent phenotype. Hence, our data indicate that nTregs effectively control exuberant immune responses by directly limiting the stimulatory capacity of DC via a sophisticated chronologic action of inhibitory signals.
Fassbender
Melanie
M
Institute for Immunology, Johannes Gutenberg-University Medical Center, Mainz, Germany.
Gerlitzki
Bastian
B
Ullrich
Nina
N
Lupp
Corinna
C
Klein
Matthias
M
Radsak
Markus P
MP
Schmitt
Edgar
E
Bopp
Tobias
T
Schild
Hansjörg
H
D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D002450:Cell Communication / Q000276:immunology*; D018920:Coculture Techniques; D000242:Cyclic AMP / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D015536:Down-Regulation; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D018664:Interleukin-12 / Q000037:antagonists & inhibitors; D051379:Mice; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
D018122:B7-1 Antigen; D051940:B7-2 Antigen; D000242:Cyclic AMP; D016753:Interleukin-10; D018664:Interleukin-12; D000093242:Interleukin-6 Inhibitors