First Author | Bogdanova D | Year | 2018 |
Journal | J Immunol | Volume | 201 |
Issue | 12 | Pages | 3580-3586 |
PubMed ID | 30397032 | Mgi Jnum | J:268258 |
Mgi Id | MGI:6269205 | Doi | 10.4049/jimmunol.1800539 |
Citation | Bogdanova D, et al. (2018) Essential Role of Canonical NF-kappaB Activity in the Development of Stromal Cell Subsets in Secondary Lymphoid Organs. J Immunol 201(12):3580-3586 |
abstractText | Organized tissue structure in the secondary lymphoid organs (SLOs) tightly depends on the development of fibroblastic stromal cells (FSCs) of mesenchymal origin; however, the mechanisms of this relationship are poorly understood. In this study, we specifically inactivated the canonical NF-kappaB pathway in FSCs in vivo by conditionally inducing IkappaBalpha mutant in a Ccl19-IkappaBSR mouse system in which NF-kappaB activity is likely to be suppressed in fetal FSC progenitors. Given that NF-kappaB activation in fetal FSCs is essential for SLO development, the animals were expected to lack SLOs. However, all SLOs were preserved in Ccl19-IkappaBSR mice. Instead, the T cell area was severely disturbed by the lack of CCL21-expressing FSCs, whereas the follicles and associated FSC networks were formed. Fate mapping revealed that IkappaBSR-expressing cells constituted only a small fraction of stromal compartment outside the follicles. Taken together, our findings indicate an essential role of the canonical NF-kappaB pathway activity in the development of three FSC subsets common to SLOs and suggest transient or stochastic CCL19 expression in FSC progenitors and a compensatory differentiation program of follicular FSCs. |