| First Author | Worthington AK | Year | 2022 |
| Journal | Development | Volume | 149 |
| Issue | 8 | PubMed ID | 35072209 |
| Mgi Jnum | J:323098 | Mgi Id | MGI:7261265 |
| Doi | 10.1242/dev.200139 | Citation | Worthington AK, et al. (2022) IL7Ralpha, but not Flk2, is required for hematopoietic stem cell reconstitution of tissue-resident lymphoid cells. Development 149(8):dev200139 |
| abstractText | Tissue-resident lymphoid cells (TLCs) span the spectrum of innate-to-adaptive immune function. Unlike traditional, circulating lymphocytes that are continuously generated from hematopoietic stem cells (HSCs), many TLCs are of fetal origin and poorly generated from adult HSCs. Here, we sought to further understand murine TLC development and the roles of Flk2 and IL7Ralpha, two cytokine receptors with known function in traditional lymphopoiesis. Using Flk2- and Il7r-Cre lineage tracing, we found that peritoneal B1a cells, splenic marginal zone B (MZB) cells, lung ILC2s and regulatory T cells (Tregs) were highly labeled. Despite high labeling, loss of Flk2 minimally affected the generation of these cells. In contrast, loss of IL7Ralpha, or combined deletion of Flk2 and IL7Ralpha, dramatically reduced the number of B1a cells, MZBs, ILC2s and Tregs, both in situ and upon transplantation, indicating an intrinsic and essential role for IL7Ralpha. Surprisingly, reciprocal transplants of wild-type HSCs showed that an IL7Ralpha-/- environment selectively impaired reconstitution of TLCs when compared with TLC numbers in situ. Taken together, our data defined Flk2- and IL7Ralpha-positive TLC differentiation paths, and revealed functional roles of Flk2 and IL7Ralpha in TLC establishment. |
