Kit ligand and Il7 differentially regulate Peyer's patch and lymph node development

Chappaz, Stéphane and Gärtner, Claudia and Rodewald, Hans-Reimer and Finke, Daniela. (2010) Kit ligand and Il7 differentially regulate Peyer's patch and lymph node development. Journal of immunology, Vol. 185, H. 6. pp. 3514-3519.

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Official URL: http://edoc.unibas.ch/dok/A6005287

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Hematopoietic lymphoid tissue inducer (LTi) cells initiate lymph node (LN) and Peyer's patch (PP) development during fetal life by inducing the differentiation of mesenchymal organizer cells. The growth factor signals underlying LTi cell development and LN and PP organogenesis remain poorly understood. LTi cells express the Il7r and the receptor tyrosine kinase Kit, whereas organizer cells express their cognate ligands. To determine the relative significance of Il7 and Kit signaling in LTi cell homeostasis and PP and LN development, we have analyzed mice deficient for Kit (Kit(W/Wv)), Il7 (Il7(-/-)), or both (Il7(-/-) Kit(W/Wv)). Unlike Kit(W/Wv) and Il7(-/-) single mutants, Il7(-/-) Kit(W/Wv) mice were almost devoid of LTi cells in their mesenteric LN anlage. This LTi deficiency was associated with a block in mesenchymal LN organizer cell generation and the absence of almost all LNs. In contrast, intestinal LTi cell numbers, PP organizer cell generation, and PP development were strongly affected by impaired Kit signaling, but were independent of Il7. Hence, Kit and Il7 act synergistically in LN organogenesis, whereas Kit signaling, but not Il7, critically regulates PP organogenesis and LTi cell numbers in the intestine. Consistent with these differential growth factor requirements for PP and LN development, PP organizer cells expressed higher Kitl and lower Il7 levels than did LN organizer cells. Collectively, these results demonstrate that Kit and Il7 differentially control PP and LN organogenesis through the local growth factor-driven regulation of LTi cell numbers.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Children's Hospital > Developmental Immunology (Finke)
UniBasel Contributors:Finke, Daniela
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Assoc. of Immunologists
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Dec 2012 13:04
Deposited On:07 Dec 2012 13:03

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