title: Adaptor protein Shc acts as an immune-regulator for the LPS-stimulated maturation of bone marrow-derived dendritic cells.
abstract: BACKGROUND
  The Shc isoforms is known to mediate immune responses and has been indicated as a negative regulator of autoimmunity and lymphocyte activation. We aimed to evaluate the immune-regulatory role of Shc in rat bone marrow-derived DCs in the maturation process triggered by LPS.
  
  
  RESULTS
  We found that, in response to LPS, expression of Shc proteins was induced and that neutralization of Shc inhibited the LPS-induced transient phosphorylation of p52Shc on pTyr239/240 in DCs of Lewis (LEW; RT1(l)) rats. Moreover, the significantly enhanced expression of IL-10 and the surface level of costimulatory molecule CD80, as well as suppressed expression of IL-6 and IL-12 in the Shc-silenced DCs were also observed. Similar IκB phosphorylation occurred in Shc-silenced DCs primed by LPS, indicating Shc is not associated with NF-κB pathway. We further demonstrate that Shc blockade on LPS-treated DCs results in significant increase of the overall STAT3 phosphorylation and the relative levels of phospho-STAT3 in the nuclear fraction. STAT3 activation by LPS with or without Shc blockade was totally abolished by SU6656, a selective Src family kinases inhibitor, underscoring the critical role of Src-mediated activation.
  
  
  CONCLUSIONS
  We conclude that Shc blockade in LPS-primed DC leads to the development of tolerogenic DC via Src-dependent STAT3 activation and that adaptor protein Shc might play a pivotal role in mediating immunogenic and tolerogenic properties of DCs.
authors: Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors: Kuang-Den
authors: KD
authors: Chen
authors: Li-Wen
authors: LW
authors: Hsu
authors: Shigeru
authors: S
authors: Goto
authors: Chin-Wei
authors: CW
authors: Yeh
authors: Toshiaki
authors: T
authors: Nakano
authors: Chia-Yun
authors: CY
authors: Lai
authors: Yen-Chen
authors: YC
authors: Chang
authors: Chiung-Hui
authors: CH
authors: Hou
authors: Chih-Chi
authors: CC
authors: Wang
authors: Yu-Fan
authors: YF
authors: Cheng
authors: King-Wah
authors: KW
authors: Chiu
authors: Chih-Che
authors: CC
authors: Lin
authors: Chao-Long
authors: CL
authors: Chen
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