Ontogeny of Stromal Organizer Cells during Lymph Node Development

Benezech, C; White, Andrea J.; Mader, Emma; Serre, Karine; Parnell, Sonia M.; Pfeffer, Klaus; Ware, Carl F.; Anderson, Graham; Caamaño, Jorge H.

doi:10.4049/jimmunol.0903113

Cited by 111 publications

(153 citation statements)

References 47 publications

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…In contrast, spleen regeneration from neonatal spleen capsule transplants relies upon LTa 1 b 2 -educated endothelial organizers, and in the absence of LT signaling shortly after birth, capsules fail to regenerate spleen tissue. Although this model accounts for a lack of tissue development observed from LT-deficient neonatal spleen capsule grafts, the proposal of an endothelial-lineage spleen organizer departs from the classical paradigm that lymphoid organizers are mesenchymally derived (32). Validation of such a model therefore requires formal identification of an endothelial spleen organizer cell population with demonstration of tissue-organizing ability.…”

Section: Discussionmentioning

confidence: 99%

Murine Spleen Tissue Regeneration from Neonatal Spleen Capsule Requires Lymphotoxin Priming of Stromal Cells

Tan

Watanabe

2014

The Journal of Immunology

View full text Add to dashboard Cite

Spleen is a tissue with regenerative capacity, which allows autotransplantation of human spleen fragments to counteract the effects of splenectomy. We now reveal in a murine model that transplant of neonatal spleen capsule alone leads to the regeneration of full spleen tissue. This finding indicates that graft-derived spleen stromal cells, but not lymphocytes, are essential components of tissue neogenesis, a finding verified by transplant and regeneration of Rag1KO spleen capsules. We further demonstrate that lymphotoxin and lymphoid tissue inducer cells participate in two key elements of spleen neogenesis, bulk tissue regeneration and white pulp organization, identifying a lymphotoxin-dependent pathway for neonatal spleen regeneration that contrasts with previously defined lymphotoxin-independent embryonic spleen organogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Murine Spleen Tissue Regeneration from Neonatal Spleen Capsule Requires Lymphotoxin Priming of Stromal Cells

Tan

Watanabe

2014

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Our data also demonstrate that aldefluor + Ly51 int gp38 + cells express significantly lower levels of CCL19 and CCL21 and express lower levels of ICAM-1 and VCAM-1 compared with aldefluor 2 Ly51 int gp38 + cells. Upregulation of VCAM-1, ICAM-1, CCL19, and CCL21 is known to characterize the LTbR-dependent differentiation of mesenchyme-derived stromal organizer cell compartment in developing lymph nodes (68,69), raising the interesting possibility that aldefluor + and aldefluor 2 subsets of Ly51 int gp38 + mesenchyme represent progressive developmental stages with a lower and higher maturation status, respectively.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Cells Regulate Retinoic Acid Receptor-Dependent Cortical Thymic Epithelial Cell Homeostasis

Sitnik

Kotarsky

White

et al. 2012

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

The vitamin A metabolite and transcriptional modulator retinoic acid (RA) is recognized as an important regulator of epithelial cell homeostasis in several tissues. Despite the known importance of the epithelial compartment of the thymus in T cell development and selection, the potential role of RA in the regulation of thymic cortical and medullary epithelial cell homeostasis has yet to be addressed. In this study, using fetal thymus organ cultures, we demonstrate that endogenous RA signaling promotes thymic epithelial cell (TEC) cell-cycle exit and restricts TEC cellularity preferentially in the cortical TEC compartment. Combined gene expression, biochemical, and functional analyses identified mesenchymal cells as the major source of RA in the embryonic thymus. In reaggregate culture experiments, thymic mesenchyme was required for RA-dependent regulation of TEC expansion, highlighting the importance of mesenchyme-derived RA in modulating TEC turnover. The RA-generating potential of mesenchymal cells was selectively maintained within a discrete Ly51intgp38+ subset of Ly51+ mesenchyme in the adult thymus, suggesting a continual role for mesenchymal cell-derived RA in postnatal TEC homeostasis. These findings identify RA signaling as a novel mechanism by which thymic mesenchyme influences TEC development.

show abstract

“…Chemokines such as CXCL13, CCL19, CCL21 and CXCL12 are involved not only in the initiation of ELF development, but also in the maintenance of the highly organized cellular architecture of established ELFs and SLOs. Given that the early clustering of LTi cells within the embryo is dependent on CXCL13, and that CXCL13 is detected early in the developing lymph nodes of LT α ‐deficient mice,46, 47 this chemokine represents a key initiator of lymphoid organogenesis that functions upstream of LT β R signalling. At ELFs, CXCL13 and CCL21 regulate B‐cell and T‐cell infiltration and segregation at ELFs 48, 49, 50.…”

Section: Homeostatic Chemokines In Elf Developmentmentioning

confidence: 99%

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

2015

View full text Add to dashboard Cite

SummaryLymphoid neogenesis is traditionally viewed as a pre‐programmed process that promotes the formation of lymphoid organs during development. Here, the spatial organization of T and B cells in lymph nodes and spleen into discrete structures regulates antigen‐specific responses and adaptive immunity following immune challenge. However, lymphoid neogenesis is also triggered by chronic or persistent inflammation. Here, ectopic (or tertiary) lymphoid organs frequently develop in inflamed tissues as a response to infection, auto‐immunity, transplantation, cancer or environmental irritants. Although these structures affect local immune responses, the contribution of these lymphoid aggregates to the underlining pathology are highly context dependent and can elicit either protective or deleterious outcomes. Here we review the cellular and molecular mechanisms responsible for ectopic lymphoid neogenesis and consider the relevance of these structures in human disease.

show abstract

Ontogeny of Stromal Organizer Cells during Lymph Node Development

Abstract: Material

Cited by 111 publications

References 47 publications

Murine Spleen Tissue Regeneration from Neonatal Spleen Capsule Requires Lymphotoxin Priming of Stromal Cells

Murine Spleen Tissue Regeneration from Neonatal Spleen Capsule Requires Lymphotoxin Priming of Stromal Cells

Mesenchymal Cells Regulate Retinoic Acid Receptor-Dependent Cortical Thymic Epithelial Cell Homeostasis

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

Contact Info

Product

Resources

About