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MiR-150 impairs inflammatory cytokine production by targeting ARRB-2 after blocking CD28/B7 costimulatory pathway
Immunology Letters
  • Wei Sang
  • Wing Yang
  • Cong Zhang
  • Dianzheng Zhang, Philadelphia College of Osteopathic Medicine
  • Cai Sun
  • Mingshan Niu
  • Zhe Zhang
  • Xiangyu Wei
  • Bin Pan
  • Wei Chen
  • Dongmei Yan
  • Lingyu Zeng
  • T. P. Loughran
  • Kailin Xu
Document Type
Article
Publication Date
11-5-2015
Abstract

MiR-150, a major modulator negatively regulating the development and differentiation of various immune cells, is widely involved in orchestrating inflammation. In transplantation immunity, miR-150 can effectively induce immune tolerance, although the underlying mechanisms have not been fully elucidated. In the current study, we found that miR-150 is elevated after blocking CD28/B7 co-stimulatory signaling pathway and impaired IL-2 production by targeting ARRB2. Further investigation suggested that miR-150 not only repressed the level of ARRB2/PDE4 directly but also prevented AKT/ARRB2/PDE4 trimer recruitment into the lipid raft by inhibiting the activities of PI3K and AKT through the cAMP-PKA-Csk signaling pathway. This leads to the interruption of cAMP degradation and subsequently results in inhibition of the NF-kB pathway and reduced production of both IL-2 and TNF. In conclusion, our study demonstrated that miR-150 can effectively prevent CD28/B7 co-stimulatory signaling transduction, decrease production of inflammatory cytokines, such as IL-2 and TNF, and elicit the induction of immune tolerance. Therefore, miR-150 could become a novel potential therapeutic target in transplantation immunology.

Comments

This article was published in Immunology Letters, November 2015.

The published version is available at http://dx.doi.org/10.1016/j.imlet.2015.11.001

Copyright © 2015 Elsevier

Citation Information
Wei Sang, Wing Yang, Cong Zhang, Dianzheng Zhang, et al.. "MiR-150 impairs inflammatory cytokine production by targeting ARRB-2 after blocking CD28/B7 costimulatory pathway" Immunology Letters (2015)
Available at: http://works.bepress.com/dianzheng_zhang/40/