| First Author | Larange A | Year | 2023 |
| Journal | Immunity | Volume | 56 |
| Issue | 9 | Pages | 2054-2069.e10 |
| PubMed ID | 37597518 | Mgi Jnum | J:340094 |
| Mgi Id | MGI:7524651 | Doi | 10.1016/j.immuni.2023.07.017 |
| Citation | Larange A, et al. (2023) A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor alpha determines T cell activation and function. Immunity |
| abstractText | Ligation of retinoic acid receptor alpha (RARalpha) by RA promotes varied transcriptional programs associated with immune activation and tolerance, but genetic deletion approaches suggest the impact of RARalpha on TCR signaling. Here, we examined whether RARalpha would exert roles beyond transcriptional regulation. Specific deletion of the nuclear isoform of RARalpha revealed an RARalpha isoform in the cytoplasm of T cells. Extranuclear RARalpha was rapidly phosphorylated upon TCR stimulation and recruited to the TCR signalosome. RA interfered with extranuclear RARalpha signaling, causing suboptimal TCR activation while enhancing FOXP3(+) regulatory T cell conversion. TCR activation induced the expression of CRABP2, which translocates RA to the nucleus. Deletion of Crabp2 led to increased RA in the cytoplasm and interfered with signalosome-RARalpha, resulting in impaired anti-pathogen immunity and suppressed autoimmune disease. Our findings underscore the significance of subcellular RA/RARalpha signaling in T cells and identify extranuclear RARalpha as a component of the TCR signalosome and a determinant of immune responses. |
