Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice.
Dendritic cells (DCs) are involved in the initiation and regulation of innate and adaptive immune responses. Several molecular mechanisms regulate these diverse DC functions, and we have previously reported that mouse dendritic cells (mDCs) can produce interleukin-2 (IL-2) in vitro and in vivo, in response to microbial activation and T-cell-mediated stimuli. This property is shared by different DC subtypes, including Langerhans cells. Here we show that, on appropriate stimulation, human DCs, both plasmacytoid and myeloid subtypes, also express IL-2. Interestingly, the production of IL-2 by myeloid DCs is induced by T-cell-mediated stimuli and depends on the presence of IL-15. The key role of this cytokine in regulating IL-2 production was also confirmed in the mouse system. In particular, we could show that DCs from IL-15-deficient mice were strongly impaired in the ability to produce IL-2 after interactions with different microbial stimuli. Our results indicate that DC-produced IL-2 is tightly coregulated with the expression of IL-15.
Feau
Sonia
S
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Milan, Italy.
Facchinetti
Valeria
V
Granucci
Francesca
F
Citterio
Stefania
S
Jarrossay
David
D
Seresini
Samantha
S
Protti
Maria Pia
MP
Lanzavecchia
Antonio
A
Ricciardi-Castagnoli
Paola
P
D000818:Animals; D019013:CD40 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019409:Interleukin-15 / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
D019013:CD40 Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D012333:RNA, Messenger