The tolerogenic peptide hCDR1 downregulates pathogenic cytokines and apoptosis and upregulates immunosuppressive molecules and regulatory T cells in peripheral blood mononuclear cells of lupus patients
| Autor: | Amir Sharabi, Edna Mozes, Ilan Asher, Uri Sela, Molly Dayan, Zev Sthoeger, Heidy Zinger |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Adult
Male medicine.medical_treatment Immunology Down-Regulation Apoptosis Biology Lymphocyte Activation T-Lymphocytes Regulatory Peripheral blood mononuclear cell Immune tolerance T-Lymphocyte Subsets Interferon Immune Tolerance medicine Humans Lupus Erythematosus Systemic Immunology and Allergy IL-2 receptor Immunosuppression Therapy Systemic lupus erythematosus Interleukin-2 Receptor alpha Subunit Interleukin FOXP3 Forkhead Transcription Factors General Medicine Middle Aged medicine.disease Complementarity Determining Regions Molecular biology Up-Regulation Cytokine Leukocytes Mononuclear Cytokines Female Peptides medicine.drug |
| Zdroj: | Human Immunology. 70:139-145 |
| ISSN: | 0198-8859 |
| DOI: | 10.1016/j.humimm.2009.01.018 |
| Popis: | A tolerogenic peptide, hCDR1, ameliorated murine lupus via the upregulation of functional regulatory cells and by immunomodulating cytokine production. In the present study we analyzed the ability of hCDR1 to similarly affect gene expression and regulatory T cells when incubated with peripheral blood mononuclear cells (PBMC) of lupus patients. To this end, peripheral blood mononuclear cells (PBMC) of 11 lupus patients and five gender- and age-matched healthy controls were cultured with hCDR1 or a control peptide. Gene expression and regulatory T-cells were assessed. hCDR1 significantly downregulated interleukin (IL)-1beta, interferon (IFN)-gamma, and IL-10 gene expression. Furthermore, hCDR1 upregulated the expression of the anti-apoptotic Bcl-xL molecule and downregulated the pro-apoptotic caspase-3, resulting in reduced rates of apoptosis. hCDR1 increased the expression of transforming growth factor (TGF)-beta, FoxP3 and the negative regulators Foxj1 and Foxo3a. No significant effects were observed using a control peptide or when PBMC of healthy donors were incubated with hCDR1. The elevated gene expression of FoxP3 was due to hCDR1-induced upregulation of TGF-beta, resulting in an increase of CD4+CD25+FoxP3+ functional, regulatory cells. The ability of the regulatory cells to diminish IFN-gamma expression and to upregulate TGF-beta was abrogated after the addition of a neutralizing anti-CD25 antibody, confirming their role in the beneficial effects of hCDR1. |
| Databáze: | OpenAIRE |
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