First published May 7, 2018 - More info
CD4+CD25+ Tregs regulate immunity, but little is known about their own regulation. We now report that the human 60-kDa heat shock protein (HSP60) acts as a costimulator of human Tregs, both CD4+CD25int and CD4+CD25hi. Treatment of Tregs with HSP60, or its peptide p277, before anti-CD3 activation significantly enhanced the ability of relatively low concentrations of the Tregs to downregulate CD4+CD25– or CD8+ target T cells, detected as inhibition of target T cell proliferation and IFN-γ and TNF-α secretion. The enhancing effects of HSP60 costimulation on Tregs involved innate signaling via TLR2, led to activation of PKC, PI3K, and p38, and were further enhanced by inhibition of ERK. HSP60-treated Tregs suppressed target T cells both by cell-to-cell contact and by secretion of TGF-β and IL-10. In addition, the expression of ERK, NF-κB, and T-bet by downregulated target T cells was inhibited. Thus, HSP60, a self-molecule, can downregulate adaptive immune responses by upregulating Tregs innately through TLR2 signaling.
Alexandra Zanin-Zhorov, Liora Cahalon, Guy Tal, Raanan Margalit, Ofer Lider, Irun R. Cohen
Original citation: J Clin Invest. 2006;116(7):2022–2032. https://doi.org/10.1172/JCI28423
Citation for this retraction: J Clin Invest. 2018;128(6):2651. https://doi.org/10.1172/JCI121856
At the request of the corresponding author, the JCI is retracting this article. The authors were recently made aware of duplicated bands in Figure 8E as well as portions of Figure 8D that were reused in another publication (Zanin-Zhorov A., et al. Cutting edge: T cells respond to lipopolysaccharide innately via TLR4 signaling. J Immunol. 2007;179(1):41–44.). After an extensive internal review, it became apparent that these duplications were introduced during figure assembly. The authors have stated that, after being made aware of the duplicated bands, they repeated the gel experiments and the results supported the conclusions of the original study. Moreover, other studies have subsequently confirmed and extended the primary conclusions of the manuscript. Nevertheless, the authors wish to retract this article because of the importance of accuracy and transparency in the published scientific literature.
The authors apologize for these errors.
See the related article at Heat shock protein 60 enhances CD4+CD25+ regulatory T cell function via innate TLR2 signaling.