| First Author | Ligons DL | Year | 2018 |
| Journal | Sci Signal | Volume | 11 |
| Issue | 545 | PubMed ID | 30154103 |
| Mgi Jnum | J:284328 | Mgi Id | MGI:6380843 |
| Doi | 10.1126/scisignal.aam8939 | Citation | Ligons DL, et al. (2018) RORgammat limits the amount of the cytokine receptor gammac through the prosurvival factor Bcl-xL in developing thymocytes. Sci Signal 11(545) |
| abstractText | The cytokine receptor subunit gammac provides critical signals for T cell survival and differentiation. We investigated the molecular mechanism that controls the cell surface abundance of gammac during T cell development in the thymus. We found that the amount of gammac was low on CD4(+)CD8(+) double-positive (DP) thymocytes before their positive selection to become mature T cells. The transcription factor RORgammat was abundant in immature DP thymocytes, and its loss resulted in an increase in the abundance of surface gammac, specifically on preselection DP cells. Rather than directly repressing expression of the gene encoding gammac, RORgammat acted through the antiapoptotic protein Bcl-xL to reduce the abundance of surface gammac, which resulted in decreased cytokine signaling and was associated with inhibition of cell metabolism and mitochondrial biogenesis. Accordingly, overexpression of Bcl-xL in RORgammat-deficient thymocytes restored the amount of surface gammac to that present on normal preselection DP cells. Together, these data highlight a previously unappreciated role for RORgammat and Bcl-xL in limiting gammac abundance at the cell surface and reveal a signaling circuit in which survival factors control cytokine signaling by limiting the abundance and surface distribution of a receptor subunit shared by several cytokines. |
