The RNA-Binding Protein KSRP Modulates Cytokine Expression of CD4+ T Cells
| Autor: | Evelyn Montermann, Andrea Pautz, Rudolf Käfer, Matthias Bros, Lisa Schmidtke, Hartmut Kleinert, Katharina Schrick |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
CD4-Positive T-Lymphocytes
0301 basic medicine lcsh:Immunologic diseases. Allergy Article Subject T cell Immunology Mice 03 medical and health sciences 0302 clinical medicine Immune system T-Lymphocyte Subsets Interferon medicine Animals Humans Immunology and Allergy RNA Messenger IL-2 receptor 3' Untranslated Regions Messenger RNA Innate immune system Chemistry Three prime untranslated region RNA-Binding Proteins General Medicine Cell biology 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Trans-Activators Cytokines lcsh:RC581-607 030217 neurology & neurosurgery CD8 Research Article Protein Binding medicine.drug |
| Zdroj: | Journal of Immunology Research, Vol 2019 (2019) Journal of Immunology Research |
| ISSN: | 2314-7156 2314-8861 |
| Popis: | The KH-type splicing regulatory protein (KSRP) is a RNA-binding protein, which regulates the stability of many mRNAs encoding immune-relevant proteins. As KSRP regulates innate immune responses, for instance by the modulation of type I interferon mRNA stability, we were interested whether knockdown of the protein (KSRP-/-) interferes with T cell activation and polarization. Polyclonally stimulated KSRP-/- CD4+ T cells proliferated at a higher extent and higher frequency and expressed the activation marker CD25 more than wild-type T cells. In supernatants of stimulated KSRP-/- CD4+ T cells, levels of IL-5, IL-9, IL-10, and IL-13 were observed to be increased compared to those of the control group. KSRP-/- CD8+ T cells showed no altered proliferative capacity upon polyclonal stimulation, but supernatants contained lower levels of interferon-γ. Similar changes in the cytokine expression patterns were also detected in T cells derived from KSRP-/- mice undergoing arthritis induction indicative of a pathophysiological role of KSRP-dependent T cell polarization. We demonstrated the direct binding of KSRP to the 3′ untranslated region of IL-13, IL-10, and IFN-γ mRNA in in vitro experiments. Moreover, since IL-4 mRNA decay was reduced in KSRP-/- CD4+ T cells, we identify KSRP as a negative regulator of IL-4 expression. These data indicate that overexpression of IL-4, which constitutes the primary inducer of Th2 polarization, may cause the Th2 bias of polyclonally stimulated KSRP-/- CD4+ T cells. This is the first report demonstrating that KSRP is involved in the regulation of T cell responses. We present strong evidence that T cells derived from KSRP-/- mice favor Th2-driven immune responses. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text