Tristetraprolin regulation of interleukin 23 mRNA stability prevents a spontaneous inflammatory disease
| Autor: | Laure Ysebrant de Lendonck, Tong Zhang, Cyril Gueydan, Félicie Sherer, Perry J. Blackshear, Gaetan Van Simaeys, Céline Molle, Stanislas Goriely, Oberdan Leo, Mathieu Andrianne |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Lipopolysaccharides
Untranslated region RNA Stability medicine.medical_treatment Immunology Tristetraprolin Bone Marrow Cells Biology Interleukin-23 Interleukin 22 Mice Immunologie Interleukin 23 medicine Animals Humans Immunology and Allergy 3' Untranslated Regions AU Rich Elements Inflammation Interleukins Interleukin-17 Brief Definitive Report Interleukin Dendritic Cells Syndrome Radiography Bone Diseases Metabolic HEK293 Cells Cytokine Interleukin-23 Subunit p19 Interleukin 12 Bone Remodeling IL17A |
| Zdroj: | The Journal of experimental medicine, 210 (9 The Journal of Experimental Medicine |
| Popis: | Interleukin (IL) 12 and IL23 are two related heterodimeric cytokines produced by antigen-presenting cells. The balance between these two cytokines plays a crucial role in the control of Th1/Th17 responses and autoimmune inflammation. Most studies focused on their transcriptional regulation. Herein, we explored the role of the adenine and uridine-rich element (ARE)-binding protein tristetraprolin (TTP) in influencing mRNA stability of IL12p35, IL12/23p40, and IL23p19 subunits. LPS-stimulated bone marrow-derived dendritic cells (BMDCs) from TTP(-/-) mice produced normal levels of IL12/23p40. Production of IL12p70 was modestly increased in these conditions. In contrast, we observed a strong impact of TTP on IL23 production and IL23p19 mRNA stability through several AREs in the 3' untranslated region. TTP(-/-) mice spontaneously develop an inflammatory syndrome characterized by cachexia, myeloid hyperplasia, dermatitis, and erosive arthritis. We observed IL23p19 expression within skin lesions associated with exacerbated IL17A and IL22 production by infiltrating γδ T cells and draining lymph node CD4 T cells. We demonstrate that the clinical and immunological parameters associated with TTP deficiency were completely dependent on the IL23-IL17A axis. We conclude that tight control of IL23 mRNA stability by TTP is critical to avoid severe inflammation. Journal Article Research Support, N.I.H. Intramural Research Support, Non-U.S. Gov't SCOPUS: ar.j info:eu-repo/semantics/published |
| Databáze: | OpenAIRE |
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