Micro-RNA-155-mediated control of heme oxygenase 1 (HO-1) is required for restoring adaptively tolerant CD4 super(+) T-cell function in rodents
T cells chronically stimulated by a persistent antigen often become dysfunctional and lose effector functions and proliferative capacity. To identify the importance of micro-RNA-155 (miR-155) in this phenomenon, we analyzed mouse miR-155-deficient CD4 super(+) T cells in a model where the chronic ex...
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Veröffentlicht in: | European journal of immunology 2015-03, Vol.45 (3), p.829-842 |
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Sprache: | eng |
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Zusammenfassung: | T cells chronically stimulated by a persistent antigen often become dysfunctional and lose effector functions and proliferative capacity. To identify the importance of micro-RNA-155 (miR-155) in this phenomenon, we analyzed mouse miR-155-deficient CD4 super(+) T cells in a model where the chronic exposure to a systemic antigen led to T-cell functional unresponsiveness. We found that miR-155 was required for restoring function of T cells after programmed death receptor 1 blockade. Heme oxygenase 1 (HO-1) was identified as a specific target of miR-155 and inhibition of HO-1 activity restored the expansion and tissue migration capacity of miR-155 super(-/-) CD4 super(+) T cells. Moreover, miR-155-mediated control of HO-1 expression in CD4 super(+) T cells was shown to sustain in vivo antigen-specific expansion and IL-2 production. Thus, our data identify HO-1 regulation as a mechanism by which miR-155 promotes T-cell-driven inflammation. |
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ISSN: | 0014-2980 1521-4141 |
DOI: | 10.1002/eji.201445066 |