| First Author | Tachibana M | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 3 | Pages | 1450-7 |
| PubMed ID | 21178013 | Mgi Jnum | J:168918 |
| Mgi Id | MGI:4939301 | Doi | 10.4049/jimmunol.1000162 |
| Citation | Tachibana M, et al. (2011) Runx1/Cbf beta2 complexes are required for lymphoid tissue inducer cell differentiation at two developmental stages. J Immunol 186(3):1450-7 |
| abstractText | Hematopoietic lymphoid tissue inducer (LTi) cells are essential for the development of secondary lymphoid tissues including lymph nodes and Peyer's patches. Two transcription factors, the helix-loop-helix inhibitor Id2 and the retinoic acid-related orphan receptor gammat (Rorgammat), have been shown to be crucial for LTi cell development. However, it remains unclear how the specification of multipotent hematopoietic progenitor cells toward the LTi lineage is programmed. In this study, we report impaired lymphoid tissue organogenesis in mice in which the function of Runx1/Cbfbeta transcription factor complexes was attenuated by the loss of either the distal promoter-derived Runx1 or Cbfbeta2 variant protein. We found that LTi progenitors in fetal liver, defined previously as a lineage marker-negative alpha4beta7 integrin (alpha4beta7)(+) IL-7R alpha-chain (IL-7Ralpha)(+) population, can be subdivided into Rorgammat-expressing IL-7Ralpha(high) cells and nonexpressing IL-7Ralpha(mid) cells. Whereas Id2 and Rorgammat are required to direct alpha4beta7(+)IL-7Ralpha(mid) cells to become alpha4beta7(+)IL-7Ralpha(high) cells, Runx1/Cbfbeta2 complexes are necessary for the emergence of alpha4beta7(+)IL-7Ralpha(mid) cells. In addition, the loss of Cbfbeta2, but not P1-Runx1, resulted in an inefficient upregulation of Rorgammat in residual alpha4beta7(+)IL-7Ralpha(+) LTi cells at anlagen. Our results thus revealed that Runx1/Cbfbeta2 complexes regulate the differentiation of LTi cells at two stages: an early specification of hematopoietic progenitors toward the LTi lineage and a subsequent activation of Rorgammat expression at anlagen. |
