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Title: Regulation of interleukin-12 and interleukin-23 production by tristetraprolin (TTP)
Authors: LOW PEY YNG
Keywords: Interleukin-12, Interleukin-23, Tristetraprolin, mRNA stability, TH17, TH1
Issue Date: 4-Jun-2012
Citation: LOW PEY YNG (2012-06-04). Regulation of interleukin-12 and interleukin-23 production by tristetraprolin (TTP). ScholarBank@NUS Repository.
Abstract: IL-12 and IL-23 form a crucial link to adaptive immunity through their ability to influence the development of TH1 and TH17 cells respectively. Despite the importance of the TH1/IL-12 and TH17/IL-23 axis in protective immunity, excessive production of IL-12 and IL-23 can be a nuisance as it leads to immunopathology. This highlights the importance of regulating IL-12 and IL-23 production and we sought to investigate the ability of the mRNA-destabilizing protein, Tristetraprolin (TTP) in regulating IL-12 and IL-23 production by bone-marrow derived dendritic cells (BMDCs). Using TTP-/- BMDCs, there was enhanced production of IL-23 and IL-12p70 as compared to WT BMDCs. This enhancement was due to enhanced mRNA stability of IL-23p19 and IL-12p35 mRNA. Coculture of naive CD4 T cells with WT and TTP-/- BMDCs revealed a role of TTP in negatively regulating TH1 responses. This enhancement of TH1 responses results from increased IL-12p70 production by TTP-/- BMDCs. Hence, our study has revealed the importance of TTP as a negative regulator of inflammatory dendritic cell function through the suppression of excessive IL-12 and IL-23 production and the inhibition of their TH1 polarizing potential.
Appears in Collections:Ph.D Theses (Open)

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