The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor.
Thymic output is a dynamic process, with high activity at birth punctuated by transient periods of involution during infection. Interferon-α (IFN-α) is a critical molecular mediator of pathogen-induced thymic involution, yet despite the importance of thymic involution, relatively little is known abo...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2012
|
| _version_ | 1797100033453064192 |
|---|---|
| author | Papadopoulou, A Dooley, J Linterman, M Pierson, W Ucar, O Kyewski, B Zuklys, S Hollander, G Matthys, P Gray, D De Strooper, B Liston, A |
| author_facet | Papadopoulou, A Dooley, J Linterman, M Pierson, W Ucar, O Kyewski, B Zuklys, S Hollander, G Matthys, P Gray, D De Strooper, B Liston, A |
| author_sort | Papadopoulou, A |
| collection | OXFORD |
| description | Thymic output is a dynamic process, with high activity at birth punctuated by transient periods of involution during infection. Interferon-α (IFN-α) is a critical molecular mediator of pathogen-induced thymic involution, yet despite the importance of thymic involution, relatively little is known about the molecular integrators that establish sensitivity. Here we found that the microRNA network dependent on the endoribonuclease Dicer, and specifically microRNA miR-29a, was critical for diminishing the sensitivity of the thymic epithelium to simulated infection signals, protecting the thymus against inappropriate involution. In the absence of Dicer or the miR-29a cluster in the thymic epithelium, expression of the IFN-α receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity. |
| first_indexed | 2024-03-07T05:32:00Z |
| format | Journal article |
| id | oxford-uuid:e296ab70-d03b-4493-a1d1-22c0a0cb5333 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:32:00Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:e296ab70-d03b-4493-a1d1-22c0a0cb53332022-03-27T10:02:37ZThe thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:e296ab70-d03b-4493-a1d1-22c0a0cb5333EnglishSymplectic Elements at Oxford2012Papadopoulou, ADooley, JLinterman, MPierson, WUcar, OKyewski, BZuklys, SHollander, GMatthys, PGray, DDe Strooper, BListon, AThymic output is a dynamic process, with high activity at birth punctuated by transient periods of involution during infection. Interferon-α (IFN-α) is a critical molecular mediator of pathogen-induced thymic involution, yet despite the importance of thymic involution, relatively little is known about the molecular integrators that establish sensitivity. Here we found that the microRNA network dependent on the endoribonuclease Dicer, and specifically microRNA miR-29a, was critical for diminishing the sensitivity of the thymic epithelium to simulated infection signals, protecting the thymus against inappropriate involution. In the absence of Dicer or the miR-29a cluster in the thymic epithelium, expression of the IFN-α receptor by the thymic epithelium was higher, which allowed suboptimal signals to trigger rapid loss of thymic cellularity. |
| spellingShingle | Papadopoulou, A Dooley, J Linterman, M Pierson, W Ucar, O Kyewski, B Zuklys, S Hollander, G Matthys, P Gray, D De Strooper, B Liston, A The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor. |
| title | The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor. |
| title_full | The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor. |
| title_fullStr | The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor. |
| title_full_unstemmed | The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor. |
| title_short | The thymic epithelial microRNA network elevates the threshold for infection-associated thymic involution via miR-29a mediated suppression of the IFN-α receptor. |
| title_sort | thymic epithelial microrna network elevates the threshold for infection associated thymic involution via mir 29a mediated suppression of the ifn α receptor |
| work_keys_str_mv | AT papadopouloua thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT dooleyj thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT lintermanm thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT piersonw thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT ucaro thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT kyewskib thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT zuklyss thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT hollanderg thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT matthysp thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT grayd thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT destrooperb thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT listona thethymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT papadopouloua thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT dooleyj thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT lintermanm thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT piersonw thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT ucaro thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT kyewskib thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT zuklyss thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT hollanderg thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT matthysp thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT grayd thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT destrooperb thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor AT listona thymicepithelialmicrornanetworkelevatesthethresholdforinfectionassociatedthymicinvolutionviamir29amediatedsuppressionoftheifnareceptor |