Chronic psychological stress impairs germinal center response by repressing miR-155
| Autor: | Yanhua Liu, Zhongyuan Wang, Wei Wang, Sun Weiguo, Lejian Lin, Yanhu Ge, Cheng Xiaoxing, Lingxia Zhang, Jianghou Hou, Xiaogang Chen, Bingfen Yang |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male Immunology Naive B cell Apoptosis Lymphocyte Activation miR-155 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Glucocorticoid receptor Corticosterone medicine Animals B cell B-Lymphocytes Endocrine and Autonomic Systems F-Box Proteins Germinal center Cell Differentiation Acquired immune system Germinal Center Cell biology DNA-Binding Proteins Mice Inbred C57BL MicroRNAs 030104 developmental biology medicine.anatomical_structure chemistry Proto-Oncogene Proteins c-bcl-6 Female 030217 neurology & neurosurgery Glucocorticoid Stress Psychological medicine.drug |
| Zdroj: | Brain, behavior, and immunity. 76 |
| ISSN: | 1090-2139 |
| Popis: | Germinal centers (GC) are vital to adaptive immunity. BCL6 and miR-155 are implicated in control of GC reaction and lymphomagenesis. FBXO11 causes BCL6 degradation through ubiquitination in B-cell lymphomas. Chronic psychological stress is known to drive immunosuppression. Corticosterone (CORT) is an adrenal hormone expressed in response to stress and can similarly impair immune functions. However, whether GC formation is disrupted by chronic psychological stress and its molecular mechanism remain to be elucidated. To address this issue, we established a GC formation model in vivo, and a GC B cell differentiation model in vitro. Comparing Naive B cells to GC B cells in vivo and in vitro, the differences of BCL6 and FBXO11 mRNA do not match the changes at the protein level and miR-155 levels that were observed. Next we demonstrated that CORT increase, induced by chronic psychological stress, reduced GC response, IgG1 antibody production and miR-155 level in vivo. The effect of chronic psychological stress can be blocked by a glucocorticoid receptor (GR) antagonist. Similarly, impaired GC B cell generation and isotope class switching were observed. Furthermore, we found that miR-155 and BCL6 expression were downregulated, but FBXO11 expression was upregulated in GC B cells treated with CORT in vitro. In addition, we demonstrated that miR-155 directly down-regulated FBXO11 expression by binding to its 3́-untranslated region. The subsequent overexpression of miR-155 significantly blocked the stress-induced impairment of GC response, due to changes in FBXO11 and BCL6 expression, as well as increased apoptosis in B cells both in vivo and in vitro. Our findings suggest perturbation of GC reaction may play a role in chronic psychological stress-induced immunosuppression through a glucocorticoid pathway, and miR-155-mediated post-transcriptional regulation of FBXO11 and BCL6 expression may contribute to the impaired GC response. |
| Databáze: | OpenAIRE |
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