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Publication : Essential Role of Canonical NF-κB Activity in the Development of Stromal Cell Subsets in Secondary Lymphoid Organs.

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.
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