Publication

Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 signaling to establish T cell niches

2026

Abstract

Compartmentalization of secondary lymphoid organs is orchestrated by specialized fibroblastic reticular cells (FRCs), which guide immune cell migration, interaction, and function. Here, we investigated the pathways driving FRC differentiation into functionally distinct subsets. A Notch signaling signature distinguished lymph node (LN) FRCs, and deletion of Notch1 and Notch2 in FRCs restricted functional specialization, particularly for T-zone FRCs (T-zone reticular cells [TRCs]). Dendritic cell (DC)-specific deletion of the Notch ligand Jagged-1 prevented Ccl19hi TRC differentiation, with homeostatic Ccr7+ DCs also being required for their maintenance. The resulting Ccl19 chemokine expression supported formation of central T-zone sub-compartments enriched in Xcr1+ DCs and CD8+ T cells. Both the spatial organization and Notch2-Jagged1 signaling activity were conserved in human LNs. Disrupting T-zone segregation via Notch2 inactivation in FRCs impaired the generation of CD8+ T cell memory precursors. Thus, Notch2-dependent TRC programming by DCs shapes distinct T-zone niches that sustain CD8+ T cell immunity.

Official source

https://infoscience.epfl.ch/entities/publication/beb0b826-d789-4bb1-97c3-e86cf6a7dc5a

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2026

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/beb0b826-d789-4bb1-97c3-e86cf6a7dc5a

About this result

Related concepts (32)

Dendritic cell

A dendritic cell (DC) is an antigen-presenting cell (also known as an accessory cell) of the mammalian immune system. A DC's main function is to process antigen material and present it on the cell surface to the T cells of the immune system. They act as messengers between the innate and adaptive immune systems. Dendritic cells are present in tissues that are in contact with the body's external environment, such as the skin (where there is a specialized dendritic cell type called the Langerhans cell), and the inner lining of the nose, lungs, stomach and intestines.

Cell-mediated immunity

Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen. In the late 19th century Hippocratic tradition medicine system, the immune system was imagined into two branches: humoral immunity, for which the protective function of immunization could be found in the humor (cell-free bodily fluid or serum) and cellular immunity, for which the protective function of immunization was associated with cells.

Innate lymphoid cell

Innate lymphoid cells (ILCs) are the most recently discovered family of innate immune cells, derived from common lymphoid progenitors (CLPs). In response to pathogenic tissue damage, ILCs contribute to immunity via the secretion of signalling molecules, and the regulation of both innate and adaptive immune cells. ILCs are primarily tissue resident cells, found in both lymphoid (immune associated), and non- lymphoid tissues, and rarely in the blood. They are particularly abundant at mucosal surfaces, playing a key role in mucosal immunity and homeostasis.

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Homeostatic mature dendritic cells instruct fibroblast specialization via Notch2 signaling to establish T cell niches

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