| First Author | Sottoriva K | Year | 2022 |
| Journal | JCI Insight | Volume | 7 |
| Issue | 9 | PubMed ID | 35349492 |
| Mgi Jnum | J:327513 | Mgi Id | MGI:7278129 |
| Doi | 10.1172/jci.insight.157015 | Citation | Sottoriva K, et al. (2022) A Notch/IL-21 signaling axis primes bone marrow T cell progenitor expansion. JCI Insight 7(9):e157015 |
| abstractText | Long-term impairment in T cell-mediated adaptive immunity is a major clinical obstacle following treatment of blood disorders with hematopoietic stem cell transplantation. Although T cell development in the thymus has been extensively characterized, there are significant gaps in our understanding of prethymic processes that influence early T cell potential. We have uncovered a Notch/IL-21 signaling axis in bone marrow common lymphoid progenitor (CLP) cells. IL-21 receptor expression was driven by Notch activation in CLPs, and in vivo treatment with IL-21 induced Notch-dependent CLP proliferation. Taking advantage of this potentially novel signaling axis, we generated T cell progenitors ex vivo, which improved repopulation of the thymus and peripheral lymphoid organs of mice in an allogeneic transplant model. Importantly, Notch and IL-21 activation were equally effective in the priming and expansion of human cord blood cells toward the T cell fate, confirming the translational potential of the combined treatment. |
