Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

D’Rozario, Joshua; Knoblich, Konstantin; Lütge, Mechthild; Shibayama, Christian Perez; Cheng, Hung‐Wei; Alexandre, Yannick O.; Roberts, David; Campos, Joana; Dutton, Emma E; Suliman, Muath; Denton, Alice E.; Turley, Shannon J.; Boyd, Richard; Mueller, Scott N.; Ludewig, Burkhard; Heng, Tracy; Fletcher, Anne

doi:10.1002/eji.202250355

Cited by 15 publications

(8 citation statements)

References 71 publications

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“…Previous work has demonstrated that FRCs in the lymph node paracortex of mice similarly express CCL2, which regulates monocyte trafficking to the paracortex (31). Furthermore, human cultured FRCs derived from lymph nodes or tonsils have also been shown to constitutively express CCL2, IL-6, CXCL8, and/or CXCL1 (15,16,28).…”

Section: Discussionmentioning

confidence: 99%

“…While there are extensive studies evaluating the function of FRCs in vivo in murine models and in vitro on TCPS, there is a need for 3D models of the human paracortex that can evaluate the trafficking of human DCs and T-cells into the lymph node. Although many molecular pathways have been shown to be conserved between human and mouse FRCs, human FRCs have been shown to differentially express a variety of cytokines and inflammatory pathways compared to mouse FRCs (13,28). Thus, in comparison to in vivo mouse models, in vitro models of the lymph node paracortex utilizing human FRCs may serve as better predictive models for preclinically testing immunotherapies targeting lymph nodes.…”

Section: Discussionmentioning

confidence: 99%

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On-chip human lymph node stromal network for evaluating dendritic cell and T-cell trafficking

Kwee

Akue

Sung

2023

Preprint

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The lymph node paracortex, also known as the T-cell zone, consists of a network of fibroblastic reticular cells (FRCs) that secrete chemokines to induce T-cell and dendritic cell trafficking into the paracortex. To model the lymph node paracortex, we utilized multi-channel microfluidic devices to engineer a 3D lymph node stromal network from human cultured FRCs embedded in a collagen I-fibrin hydrogel. In the hydrogel, the FRCs self-assembled into an interconnected network, secreted the extracellular matrix proteins entactin, collagen IV, and fibronectin, as well as expressed an array of immune cell trafficking chemokines. Although the engineered FRC network did not secrete characteristic CCR7-ligand chemokines (i.e. CCL19 and CCL21), human primary TNF-α matured monocyte-derived dendritic cells, CD45RA+T-cells, and CD45RA-T-cells migrated toward the lymph node stromal network to a greater extent than toward a blank hydrogel. Furthermore, the FRCs co-recruited dendritic cells and antigen-specific T-cells into the lymph node stromal network. This engineered lymph node stromal network may help evaluate how human dendritic cells and T-cells migrate into the lymph node paracortex via CCR7-independent mechanisms.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

On-chip human lymph node stromal network for evaluating dendritic cell and T-cell trafficking

Kwee

Akue

Sung

2023

Preprint

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“…They are characterized by the expression of smooth muscle actin and desmin. The fibroblastic reticular cell tumor is thought to be a neoplasm originating from putative stromal fibroblastic reticular cells [3,[20][21][22].…”

Section: Fibroblastic Reticular Cellsmentioning

confidence: 99%

Pathologic characteristics of histiocytic and dendritic cell neoplasms

Yoon

2024

Blood Res.

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Histiocytic and dendritic cell neoplasms comprise diverse tumors originating from the mononuclear phagocytic system, which includes monocytes, macrophages, and dendritic cells. The 5th edition of the World Health Organization (WHO) classification updating the categorization of these tumors, reflecting a deeper understanding of their pathogenesis.In this updated classification system, tumors are categorized as Langerhans cell and other dendritic cell neoplasms, histiocyte/macrophage neoplasms, and plasmacytoid dendritic cell neoplasms. Follicular dendritic cell neoplasms are classified as mesenchymal dendritic cell neoplasms within the stroma-derived neoplasms of lymphoid tissues.Each subtype of histiocytic and dendritic cell neoplasms exhibits distinct morphological characteristics. They also show a characteristic immunophenotypic profile marked by various markers such as CD1a, CD207/langerin, S100, CD68, CD163, CD4, CD123, CD21, CD23, CD35, and ALK, and hematolymphoid markers such as CD45 and CD43. In situ hybridization for EBV-encoded small RNA (EBER) identifies a particular subtype. Immunoprofiling plays a critical role in determining the cell of origin and identifying the specific subtype of tumors. There are frequent genomic alterations in these neoplasms, especially in the mitogen-activated protein kinase pathway, including BRAF (notably BRAF V600E), MAP2K1, KRAS, and NRAS mutations, and ALK gene translocation.This review aims to offer a comprehensive and updated overview of histiocytic and dendritic cell neoplasms, focusing on their ontogeny, morphological aspects, immunophenotypic profiles, and molecular genetics. This comprehensive approach is essential for accurately differentiating and classifying neoplasms according to the updated WHO classification.

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“…Whether and to what extent MRC-derived DLL1 or other notch ligands affect myeloid cell homeostasis in the splenic marginal zone is, however, still unresolved. In contrast, the contribution of the macrophage master regulator colony-stimulating factor 1 (CSF1, macrophage colony-stimulating factor) for balancing of myeloid cell populations has recently been clarified ( Bellomo et al, 2020 ; D’Rozario et al, 2023 ; Fig. 2 a ).…”

Section: Conserved Frc Niche Functions Across Lymphoid Organsmentioning

confidence: 99%

“…2 a ). CSF1 is produced by human and mouse LN FRCs and has been shown to stimulate macrophage development and activation in vitro ( D’Rozario et al, 2023 ). In the murine spleen, CSF1 generated by Ccl19-Cre + MRCs appears to be essential for the maintenance of CD169 + metallophilic macrophages ( Bellomo et al, 2020 ).…”

Section: Conserved Frc Niche Functions Across Lymphoid Organsmentioning

confidence: 99%

Protective fibroblastic niches in secondary lymphoid organs

De Martin,

Stanossek,

Pikor

et al. 2023

Journal of Experimental Medicine

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Fibroblastic reticular cells (FRCs) are specialized fibroblasts of secondary lymphoid organs that provide the structural foundation of the tissue. Moreover, FRCs guide immune cells to dedicated microenvironmental niches where they provide lymphocytes and myeloid cells with homeostatic growth and differentiation factors. Inflammatory processes, including infection with pathogens, induce rapid morphological and functional adaptations that are critical for the priming and regulation of protective immune responses. However, adverse FRC reprogramming can promote immunopathological tissue damage during infection and autoimmune conditions and subvert antitumor immune responses. Here, we review recent findings on molecular pathways that regulate FRC–immune cell crosstalk in specialized niches during the generation of protective immune responses in the course of pathogen encounters. In addition, we discuss how FRCs integrate immune cell–derived signals to ensure protective immunity during infection and how therapies for inflammatory diseases and cancer can be developed through improved understanding of FRC–immune cell interactions.

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Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

Cited by 15 publications

References 71 publications

On-chip human lymph node stromal network for evaluating dendritic cell and T-cell trafficking

On-chip human lymph node stromal network for evaluating dendritic cell and T-cell trafficking

Pathologic characteristics of histiocytic and dendritic cell neoplasms

Protective fibroblastic niches in secondary lymphoid organs

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