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Faculty of 1000 Biology | Distinct signal codes generate dendritic cell.
http://f1000biology.com/article/id/3580968/evaluation Welcome Kazu Arima
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Distinct signal codes generate dendritic cell functional plasticity.
Arima K, Watanabe N, Hanabuchi S, Chang M, Sun SC, Liu YJ
F1000 Factor 6.0
Sci Signal 2010 3(105):ra4 [abstract on PubMed] [citations on Google Scholar]
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Selected by | Bryan D Bel and Steve Ziegler
Evaluated 15 Jun 2010
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Bryan D Bell and
Steve Ziegler
This is the first study to show that thymic stromal lymphopoietin (TSLP)
activates canonical Jak/Stat and distinct nuclear factor kappaB (NF-kappaB)
signalling pathways in human primary myeloid dendritic cells (mDC) in order
to promote a T helper 2 response by the immune system.
Surprisingly, human TSLP promoted broad and sustained Jak-1 and -2 activation, which further lead to the phosphorylation of Stat-1, -3, -4, -5 and-6. Furthermore, while TSLP signalling led to comparable nuclear translocationof the NF-kappaB subunits p52 and RelB as other activators of mDCs, such asPoly(I:C), R848 and CD40L, it also activated p50, which gives it the uniqueability to upregulate OX40L on mDCs. The results presented in this paperfurther emphasize that proximal and distal signalling events downstream ofthe TSLPR between mice and humans vary greatly. To date, no evidence hasbeen presented in which murine TSLP requires JAK signalling to activate Stat-5or exert its biological effects, and no other Stat proteins are phosphorylated inresponse to mouse TSLP {1}. Lastly, while the authors show that TSLP cannotact as a dominant negative in the suppression of interleukin (IL)-12 signallingin primary human mDCs in response to Toll-like receptor signalling, murineTSLP clearly inhibits lipopolysaccharide-induced IL-12/23p40 production inmurine DCs {2}. This study is an important step in determining the molecularmechanisms activated by human TSLP, and it will be very important todetermine exactly how human and murine TSLP differ in orchestrating theirbiological and biochemical effects on the immune system. This will further leadto the ability to develop and test drugs aimed at modulating TSLP signalling inthe treatment of atopic diseases.
References: {1} Rochman and Leonard, Curr Opin Pharmacol 2008, 8:249-54[PMID:18450510]. {2} Taylor et al. J Exp Med 2009, 206:655-67 [PMID:19273626].
Competing interests: None declared
Evaluated 15 Jun 2010
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How to cite the Faculty of 1000 Biology evaluation(s) for this paper
1) To cite all the evaluations for this article:
Faculty of 1000 Biology | Distinct signal codes generate dendritic cell.
http://f1000biology.com/article/id/3580968/evaluation Faculty of 1000 Biology: evaluations for Arima K et al Sci Signal 2010 3 (105) :ra4 http://f1000biology.com/article/id/3580968/evaluation 2) To cite an evaluation by a specific Faculty member:
Steve Ziegler: Faculty of 1000 Biology, 15 Jun 2010 http://f1000biology.com/article/id/3580968/evaluation 1999-2010 Faculty of 1000 Ltd unless otherwise stated. < [email protected] > Terms and conditions Legal info

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