1. Academic Validation
  2. Caerulomycin A enhances transforming growth factor-β (TGF-β)-Smad3 protein signaling by suppressing interferon-γ (IFN-γ)-signal transducer and activator of transcription 1 (STAT1) protein signaling to expand regulatory T cells (Tregs)

Caerulomycin A enhances transforming growth factor-β (TGF-β)-Smad3 protein signaling by suppressing interferon-γ (IFN-γ)-signal transducer and activator of transcription 1 (STAT1) protein signaling to expand regulatory T cells (Tregs)

  • J Biol Chem. 2014 Jun 20;289(25):17515-28. doi: 10.1074/jbc.M113.545871.
Rama Krishna Gurram 1 Weshely Kujur 1 Sudeep K Maurya 1 Javed N Agrewala 2
Affiliations

Affiliations

  • 1 From the Immunology Laboratory, Institute of Microbial Technology (Council of Scientific and Industrial Research), Chandigarh 160036, India.
  • 2 From the Immunology Laboratory, Institute of Microbial Technology (Council of Scientific and Industrial Research), Chandigarh 160036, India javed@imtech.res.in.
Abstract

Cytokines play a very important role in the regulation of immune homeostasis. Regulatory T cells (Tregs) responsible for the generation of peripheral tolerance are under the tight regulation of the cytokine milieu. In this study, we report a novel role of a bipyridyl compound, Caerulomycin A (CaeA), in inducing the generation of Tregs. It was observed that CaeA substantially up-regulated the pool of Tregs, as evidenced by an increased frequency of CD4(+) Foxp3(+) cells. In addition, CaeA significantly suppressed the number of Th1 and Th17 cells, as supported by a decreased percentage of CD4(+)/IFN-γ(+) and CD4(+)/IL-17(+) cells, respectively. Furthermore, we established the mechanism and observed that CaeA interfered with IFN-γ-induced STAT1 signaling by augmenting SOCS1 expression. An increase in the TGF-β-mediated SMAD3 activity was also noted. Furthermore, CaeA rescued Tregs from IFN-γ-induced inhibition. These results were corroborated by blocking SMAD3 activity, which abolished the CaeA-facilitated generation of Tregs. In essence, our results indicate a novel role of CaeA in inducing the generation of Tregs. This finding suggests that CaeA has enough potential to be considered as a potent future drug for the treatment of autoimmunity.

Keywords

Immunology; Immunosuppression; Immunotherapy; SMAD Transcription Factor; STAT Transcription Factor; T Cell.

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