| First Author | Cui G | Year | 2020 |
| Journal | J Immunol | Volume | 204 |
| Issue | 4 | Pages | 844-857 |
| PubMed ID | 31924648 | Mgi Jnum | J:284111 |
| Mgi Id | MGI:6388957 | Doi | 10.4049/jimmunol.1900456 |
| Citation | Cui G, et al. (2020) IL-7R-Dependent Phosphatidylinositol 3-Kinase Competes with the STAT5 Signal to Modulate T Cell Development and Homeostasis. J Immunol 204(4):844-857 |
| abstractText | T cell development and homeostasis requires IL-7R alpha-chain (IL-7Ralpha) signaling. Tyrosine Y449 of the IL-7Ralpha is essential to activate STAT5 and PI3K, whereas PI3K recruitment requires IL-7Ralpha methionine M452. How IL-7Ralpha activates and regulates both signaling pathways differentially remains unclear. To characterize differential signaling, we established two lines of IL-7Ralpha mutant mice: IL-7R-Y449F mice and IL-7R-M452L mice. IL-7R-Y449F mice showed decreased PI3K and STAT5 signals, whereas IL-7R-M452L mice showed decreased PI3K but significantly increased STAT5 signaling, owing to a competition between PI3K and STAT5 signaling through Y449 of IL-7Ralpha. The number of T, B, and mature innate lymphoid cells were markedly reduced in IL-7R-Y449F mice, whereas IL-7R-M452L mice showed impaired early T cell development and memory precursor effector T cell maintenance with the downregulation of transcription factor T cell factor-1. Peripheral T cell numbers increased in IL-7R-M452L mice with enhanced survival and homeostatic proliferation. Furthermore, although wild type and IL-7R-Y449F mice showed comparable Th1/Th2 differentiation, IL-7R-M452L mice exhibited impaired Th17 differentiation. We conclude that PI3K competes with STAT5 under IL-7Ralpha and maintains an appropriate signal balance for modulating T cell development and homeostasis. To our knowledge, this study provides a new insight into complex regulation of IL-7Ralpha signaling, which supports immune development and responses. |
