ArticleMolecular and cellular biology2015
The calcineurin-NFAT axis controls allograft immunity in myeloid-derived suppressor cells through reprogramming T cell differentiation.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Shifting phenotype and differentiation of CD11bInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Emerging roles of MITF as a crucial regulator of immunity.Experimental & molecular medicine · 2024Review
- Cell-free chromatin immunoprecipitation to detect molecular pathways in heart transplantation.Life science alliance · 2023Article
- Cell-free Chromatin Immunoprecipitation to detect molecular pathways in Physiological and Disease States.bioRxiv : the preprint server for biology · 2023Article
- Article
- Single-cell transcriptomics reveals a senescence-associated IL-6/CCR6 axis driving radiodermatitis.EMBO molecular medicine · 2022Article
- Pharmacological modulation of myeloid-derived suppressor cells to dampen inflammation.Frontiers in immunology · 2022Review
- TGF-β Enhances Immunosuppression of Myeloid-Derived Suppressor Cells to Induce Transplant Immune Tolerance Through Affecting Arg-1 Expression.Frontiers in immunology · 2022Article
- Aging Affects the Role of Myeloid-Derived Suppressor Cells in Alloimmunity.Frontiers in immunology · 2022Review
- Functional differentiation and regulation of follicular T helper cells in inflammation and autoimmunity.Immunology · 2021Review
- Inhibition of Calcineurin/NFAT Signaling Blocks Oncogenic H-Ras Induced Autophagy in Primary Human Keratinocytes.Frontiers in cell and developmental biology · 2021Article
- Immunosuppression Affects Neutrophil Functions: Does Calcineurin-NFAT Signaling Matter?Frontiers in immunology · 2021Review
- Myeloid-Derived Suppressor Cells Are Increased in Lung Transplant Recipients and Regulated by Immunosuppressive Therapy.Frontiers in immunology · 2021Article
- Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?Frontiers in immunology · 2021Review
- Review
- Donor myeloid derived suppressor cells (MDSCs) prolong allogeneic cardiac graft survival through programming of recipient myeloid cells in vivo.Scientific reports · 2020Article
- Deletion of Calcineurin Promotes a Protumorigenic Fibroblast Phenotype.Cancer research · 2019Article
- Myeloid-Derived Suppressor Cells in Lung Transplantation.Frontiers in immunology · 2019Article
- Myeloid-derived suppressor cells increase and inhibit donor-reactive T cell responses to graft intestinal epithelium in intestinal transplant patients.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
While cyclosporine (CsA) inhibits calcineurin and is highly effective in prolonging rejection for transplantation patients, the immunological mechanisms remain unknown. Herein, the role of calcineurin signaling was investigated in a mouse allogeneic skin transplantation model. The calcineurin inhibitor CsA significantly ameliorated allograft rejection. In CsA-treated allograft recipient mice, CD11b(+) Gr1(+) myeloid-derived suppressor cells (MDSCs) were functional suppressive immune modulators that resulted in fewer gamma interferon (IFN-γ)-producing CD8(+) T cells and CD4(+) T cells (T(H)1 T helper cells) and more interleukin 4 (IL-4)-producing CD4(+) T cells (T(H2)) and prolonged allogeneic skin graft survival. Importantly, the expression of NFATc1 is significantly diminished in the CsA-induced MDSCs. Blocking NFAT (nuclear factor of activated T cells) with VIVIT phenocopied the CsA effects in MDSCs and increased the suppressive activities and recruitment of CD11b(+) Gr1(+) MDSCs in allograft recipient mice. Mechanistically, CsA treatment enhanced the expression of indoleamine 2,3-dioxygenase (IDO) and the suppressive activities of MDSCs in allograft recipients. Inhibition of IDO nearly completely recovered the increased MDSC suppressive activities and the effects on T cell differentiation. The results of this study indicate that MDSCs are an essential component in controlling allograft survival following CsA or VIVIT treatment, validating the calcineurin-NFAT-IDO signaling axis as a potential therapeutic target in transplantation.
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