| First Author | Wong VA | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1369818 | PubMed ID | 38812502 |
| Mgi Jnum | J:349352 | Mgi Id | MGI:7644332 |
| Doi | 10.3389/fimmu.2024.1369818 | Citation | Wong VA, et al. (2024) IL-2Ralpha KO mice exhibit maternal microchimerism and reveal nuclear localization of IL-2Ralpha in lymphoid and non-lymphoid cells. Front Immunol 15:1369818 |
| abstractText | INTRODUCTION: IL-2Ralpha knock out (KO) mice have been instrumental to discovering the immunoregulatory properties of IL-2Ralpha. While initially thought of only as a stimulatory cytokine, IL-2 and IL-2Ralpha KO mice revealed that this cytokine-receptor system controls immune responses through restimulation-induced cell death and by promoting the survival of T regulatory cells. Although described mostly in the context of lymphocytes, recent studies by our laboratory showed that IL-2R is expressed in smooth muscle cells. Given this finding, we sought to use IL-2Ralpha KO to determine the function of this receptor in vascular smooth muscle cells. Surprisingly, we found that IL-2Ralpha KO vascular smooth muscle cells had detectable IL-2Ralpha. METHODS: We used multiple gene and protein-based methods to determine why IL-2Ralpha KO vascular smooth muscle cells exhibited IL-2Ralpha protein. These methods included: genomic sequencing, assessing cells and tissues for evidence of maternal microchimerism, and determining the half-life of IL-2Ralpha protein. RESULTS: Our studies demonstrated the following: (1) in addition to the cell surface, IL-2Ralpha is localized to the nucleus; (2) the genetic deletion of IL-2Ralpha is intact in IL-2Ralpha KO mice; (3) both IL-2Ralpha KO and WT tissues show evidence of maternal microchimerism, the likely source of IL-2Ralpha (4) IL-2Ralpha is transmitted between cells; (5) IL-2Ralpha has a long half-life; and (6) nuclear IL-2Ralpha contributes to the regulation of cell proliferation and size. CONCLUSION: Our findings suggest that the phenotype of complete IL-2Ralpha loss is more severe than demonstrated by IL-2Ralpha KO mice, and that IL-2Ralpha plays a here-to-fore unrecognized role in regulating cell proliferation in non-lymphoid cells. |
