Stromal cells as trend-setters for cells migrating into the lymph node

Büettner, Manuela; Dittrich–Breiholz, Oliver; Falk, Christine S.; Lochner, Matthias; Smoczek, Anna; Menzel, Franziska; Bornemann, Melanie; Bode, Ulrike

doi:10.1038/mi.2014.97

Cited by 6 publications

(4 citation statements)

References 39 publications

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“…MADCAM-1 is a mucosal adhesion molecule that binds surface proteins on T lymphocytes, thereby guiding them into lymphoid tissue for activation [ 23 ]. Although MADCAM-1 has been studied primarily in the context of gastrointestinal lymphoid tissue [ 24 ], queries of the GTEx database reveal robust MADCAM-1 expression in several other organs, including the thyroid and brain. In line with these findings, our data indicates that MADCAM-1 expression was increased in late recurring VS.…”

Section: Discussionmentioning

confidence: 99%

Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology

Amit

Xie

Gleber‐Netto

et al. 2022

J Exp Clin Cancer Res

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Background The management of sub-totally resected sporadic vestibular schwannoma (VS) may include observation, re-resection or irradiation. Identifying the optimal choice can be difficult due to the disease’s variable progression rate. We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression. Methods We used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or non-progressing VS. Results Rapidly progressing VS was distinctly enriched in CD4+, CD8+, CD20+, and CD68+ immune cells. RNA data indicated the upregulation of anti-viral innate immune response and T-cell senescence. K − Top Scoring Pair analysis identified 6 pairs of immunosenescence-related genes (CD38-KDR, CD22-STAT5A, APCS-CXCR6, MADCAM1-MPL, IL6-NFATC3, and CXCL2-TLR6) that had high sensitivity (100%) and specificity (78%) for identifying rapid VS progression. Conclusion Rapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS.

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Section: Discussionmentioning

confidence: 99%

Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology

Amit

Xie

Gleber‐Netto

et al. 2022

J Exp Clin Cancer Res

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“…In section 1.1 Preparation of mouse splenic singlecell suspensions, we described how to prepare single-cell suspensions from mouse spleen. Following their preparation, 10×10 6 cells are transferred to a 96-well V-bottom plate to perform antibody stainings enabling flow cytometric analysis. Expected cell counts are depicted in Table 3 of section 1.1 Preparation of mouse splenic single-cell suspensions.…”

Section: Antibody Staining Of Splenic Single-cell Suspensions For Flo...mentioning

confidence: 99%

“…Thus, it is of utmost importance to avoid DC activation during isolation. In the following, we provide an optimized, mild but efficient protocol for the isolation of DC containing single-cell sus- Owing to a very different set of environmental challenges in the intestine, intestine-associated mesenteric lymph nodes, including DC phenotype and function, differ from regular lymph nodes, thus requiring a separate analysis [1, [6][7][8]. For detailed protocols enabling the generation of single-cell suspensions from mouse mesenteric lymph nodes (MLN) and the flow cytometric analysis of MLN DC, please directly refer to the article "Guidelines for DC preparation and flow cytometry analysis of mouse non-lymphoid tissues" to Sections 1.2 Preparation of single-cell suspensions from mouse intestinal tract and 2.2 Flow cytometry analysis of DC subsets in the mouse intestinal tissue [9].…”

Section: Introductionmentioning

confidence: 99%

Guidelines for DC preparation and flow cytometry analysis of mouse lymphohematopoietic tissues

et al. 2022

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This article is part of the Dendritic Cell Guidelines article series, which provides a collection of state‐of‐the‐art protocols for the preparation, phenotype analysis by flow cytometry, generation, fluorescence microscopy, and functional characterization of mouse and human DC from lymphoid organs, and various non‐lymphoid tissues. Within this chapter, detailed protocols are presented that allow for the generation of single‐cell suspensions from mouse lymphohematopoietic tissues including spleen, peripheral lymph nodes, and thymus, with a focus on the subsequent analysis of DC by flow cytometry. However, prepared single‐cell suspensions can be subjected to other applications including sorting and cellular enrichment procedures, RNA sequencing, Western blotting, and many more. While all protocols were written by experienced scientists who routinely use them in their work, this article was also peer‐reviewed by leading experts and approved by all co‐authors, making it an essential resource for basic and clinical DC immunologists.

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“…Plasma cells in the mLN were found to predominantly produce IgA, whereas plasma cells induced in peripheral lymph nodes (pLN) were mainly IgG producing cells ( 12 ). Microarray-, RNAseq-, and protein analyses revealed various expression differences between stromal cells draining different areas, but also between distinct stromal cell subpopulations ( 13 – 17 ). All these variations result normally in an optimal immune response to protect the specific draining area of the LN.…”

Section: Introductionmentioning

confidence: 99%

Lymph Node Stromal Cells From Different Draining Areas Distinctly Regulate the Development of Chronic Intestinal Inflammation

et al. 2021

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The balance between the responsiveness of the intestinal immune system and the gut environment is fundamental for the maintenance of intestinal homeostasis, which is required for an adequate recognition of entering antigens. The disruption of this homeostasis by exaggerated immune response to harmless antigens can lead to the development of intestinal disorders such as inflammatory bowel disease. Stromal cells are sessile non-hematopoietic cells that build the backbone of the lymph node, an important site for the immune response induction, but also contribute to immune response and tolerance induction. However, the knowledge about the role of stromal cells in the regulation of inflammatory responses is still limited. Therefore, in this study we analyzed the influence of stromal cells on the development of chronic intestinal inflammation. Here, we show that intestinal inflammation alters the immune activation of the mesenteric lymph node-derived stromal cells. Podoplanin+ and CD21/35+ stromal cells showed increased expression of MHC class II molecules, but CD106 expression on CD21/35+ cells was reduced. Stromal cells secreted cytokines and chemokines such as CCL7 and CXCL16 influenced the gut-homing phenotype and proliferation of CD4+ and CD8+ T cells. Furthermore, stromal cells of peripheral lymph nodes transplanted into the mesentery attenuated colitis severity in B6-Il10-/- mice. The reduced colitis severity in these mice was associated with increased expression of IL4 and distinct activation pattern of stromal cells derived from transplanted peripheral lymph nodes. Altogether, our results demonstrate that lymph node stromal cells impact development of chronic colitis via T cell induction. Moreover, lymph node stromal cells from different draining area due to neonatally imprinted processes distinctly regulate the induction of immune responses.

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Stromal cells as trend-setters for cells migrating into the lymph node

Cited by 6 publications

References 39 publications

Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology

Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology

Guidelines for DC preparation and flow cytometry analysis of mouse lymphohematopoietic tissues

Lymph Node Stromal Cells From Different Draining Areas Distinctly Regulate the Development of Chronic Intestinal Inflammation

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