PMID- 23835553
OWN - NLM
STAT- MEDLINE
DCOM- 20140408
LR  - 20211203
IS  - 1440-1711 (Electronic)
IS  - 0818-9641 (Linking)
VI  - 91
IP  - 7
DP  - 2013 Aug
TI  - Rapamycin and omega-1: mTOR-dependent and -independent Th2 skewing by human 
      dendritic cells.
PG  - 486-9
LID - 10.1038/icb.2013.31 [doi]
AB  - Recent reports have attributed an immunoregulatory role to the mammalian target 
      of rapamycin (mTOR), a key serine/threonine protein kinase integrating input from 
      growth factors and nutrients to promote cell growth and differentiation. In the 
      present study, we investigated the role of the mTOR pathway in Th2 induction by 
      human monocyte-derived dendritic cells (moDCs). Using a co-culture system of 
      human lipopolysaccharide (LPS)-matured moDCs and allogeneic naive CD4(+) T cells, 
      we show that inhibition of mTOR by the immunosuppressive drug rapamycin reduced 
      moDC maturation and promoted Th2 skewing. Next, we investigated whether antigens 
      from helminth parasites, the strongest natural inducers of Th2 responses, 
      modulate moDCs via the mTOR pathway. In contrast to rapamycin, neither 
      Schistosoma mansoni-soluble egg antigens (SEA) nor its major immunomodulatory 
      component omega-1 affected the phosphorylation of S6 kinase (S6K) and 4E-binding 
      protein 1 (4E-BP1), downstream targets of mTORC1. Finally, we found that the 
      effects of rapamycin and SEA/omega-1 on Th2 skewing were additive, suggesting two 
      distinct underlying molecular mechanisms. We conclude that conditioning human 
      moDCs to skew immune responses towards Th2 can be achieved via an mTOR-dependent 
      and -independent pathway triggered by rapamycin and helminth antigens, 
      respectively.
FAU - Hussaarts, Leonie
AU  - Hussaarts L
AD  - Department of Parasitology, Leiden University Medical Center, Leiden, The 
      Netherlands.
FAU - Smits, Hermelijn H
AU  - Smits HH
FAU - Schramm, Gabriele
AU  - Schramm G
FAU - van der Ham, Alwin J
AU  - van der Ham AJ
FAU - van der Zon, Gerard C
AU  - van der Zon GC
FAU - Haas, Helmut
AU  - Haas H
FAU - Guigas, Bruno
AU  - Guigas B
FAU - Yazdanbakhsh, Maria
AU  - Yazdanbakhsh M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130709
PL  - United States
TA  - Immunol Cell Biol
JT  - Immunology and cell biology
JID - 8706300
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Antigens, Helminth)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Egg Proteins)
RN  - 0 (Helminth Proteins)
RN  - 0 (Isoantigens)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Phosphoproteins)
RN  - 0 (gp50 protein, Schistosoma)
RN  - 0 (omega-1 antigen, Schistosoma mansoni)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/metabolism
MH  - Animals
MH  - Antigens, Helminth/immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cell Cycle Proteins
MH  - Cell Differentiation/drug effects
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Dendritic Cells/*immunology
MH  - Egg Proteins/immunology
MH  - Helminth Proteins/immunology
MH  - Humans
MH  - Isoantigens/immunology
MH  - Lipopolysaccharides/immunology
MH  - Phosphoproteins/metabolism
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Schistosoma mansoni/*immunology
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/immunology/*metabolism
MH  - Th1-Th2 Balance/drug effects
EDAT- 2013/07/10 06:00
MHDA- 2014/04/09 06:00
CRDT- 2013/07/10 06:00
PHST- 2013/02/01 00:00 [received]
PHST- 2013/05/17 00:00 [revised]
PHST- 2013/06/03 00:00 [accepted]
PHST- 2013/07/10 06:00 [entrez]
PHST- 2013/07/10 06:00 [pubmed]
PHST- 2014/04/09 06:00 [medline]
AID - icb201331 [pii]
AID - 10.1038/icb.2013.31 [doi]
PST - ppublish
SO  - Immunol Cell Biol. 2013 Aug;91(7):486-9. doi: 10.1038/icb.2013.31. Epub 2013 Jul 
      9.