Stromal cells in tertiary lymphoid structures: Architects of autoimmunity

Asam, Saba; Nayar, Saba; Gardner, David H.; Barone, Francesca

doi:10.1111/imr.12987

Cited by 21 publications

(24 citation statements)

References 110 publications

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“…This vMIP-II-based PET nanoprobe, known as 64 Cu-DOTA-vMIP-II, was revealed to be targeting endothelial CXCR4 in Apoe −/− mice. In addition, studies with 64 Cu-DOTA-vMIP-II demonstrated an increased CXCR4 expression on plaque margins experiencing a high degree of endothelial dysfunction, thus exposing this tracer as a diagnostic tool for injuries to the endothelium [171]. Other chemokine receptors exploited for imaging of atherosclerotic lesions include CCR5 and CCR2 [172].…”

Section: Imaging As a Diagnostic Tool In Atherosclerosismentioning

confidence: 99%

“…Besides the above described pathways, chemokines and chemokine receptors also play an important role in atherosclerosis development on other fronts. Under chronic inflammatory conditions, resident stromal mesenchymal cells (MSCs) are activated by proinflammatory molecules, including IL-17, IL-23, LTα 1 β 2 , TNFα, and chemokines, including CCL2, CCL3, CXCL9, CXCL10, and CXCL11 [64][65][66][67]. These molecules are produced by lymphotoxinα1β2-expressing hematopoietic lymphoid tissue inducer (LTi) cells [68].…”

Section: Initiation Of Atherosclerosismentioning

confidence: 99%

“…Another tracer, developed for PET imaging, is based on viral macrophage inflammatory protein 2 (vMIP-II), a ligand which is able to bind to multiple chemokine receptors, including CCR2, CCR3, CCR5, ACKR3, CX 3 CR1, and CXCR4 [171]. This vMIP-II-based PET nanoprobe, known as 64 Cu-DOTA-vMIP-II, was revealed to be targeting endothelial CXCR4 in Apoe −/− mice. In addition, studies with 64 Cu-DOTA-vMIP-II demonstrated an increased CXCR4 expression on plaque margins experiencing a high degree of endothelial dysfunction, thus exposing this tracer as a diagnostic tool for injuries to the endothelium [171].…”

Section: Imaging As a Diagnostic Tool In Atherosclerosismentioning

confidence: 99%

“…In addition, preinjections with DAPTA, a CCR5 binding peptide, decreased the uptake of 111 In-DOTA-DAPTA, thereby showing that 111 In-DOTA-DAPTA specifically targets CCR5 [168]. In the case of CCR2, a clinical trial recently began recruiting participants and aims to evaluate arterial atherosclerosis using the imaging agent 64 Cu-DOTA-ECL1i (ClinicalTrials.gov (accessed on 22 July 2021) Identifier: NCT04537403).…”

Section: Imaging As a Diagnostic Tool In Atherosclerosismentioning

confidence: 99%

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Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential

Márquez

Vorst

Maas

2021

JCM

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The search to improve therapies to prevent or treat cardiovascular diseases (CVDs) rages on, as CVDs remain a leading cause of death worldwide. Here, the main cause of CVDs, atherosclerosis, and its prevention, take center stage. Chemokines and their receptors have long been known to play an important role in the pathophysiological development of atherosclerosis. Their role extends from the initiation to the progression, and even the potential regression of atherosclerotic lesions. These important regulators in atherosclerosis are therefore an obvious target in the development of therapeutic strategies. A plethora of preclinical studies have assessed various possibilities for targeting chemokine signaling via various approaches, including competitive ligands and microRNAs, which have shown promising results in ameliorating atherosclerosis. Developments in the field also include detailed imaging with tracers that target specific chemokine receptors. Lastly, clinical trials revealed the potential of various therapies but still require further investigation before commencing clinical use. Although there is still a lot to be learned and investigated, it is clear that chemokines and their receptors present attractive yet extremely complex therapeutic targets. Therefore, this review will serve to provide a general overview of the connection between various chemokines and their receptors with atherosclerosis. The different developments, including mouse models and clinical trials that tackle this complex interplay will also be explored.

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Section: Imaging As a Diagnostic Tool In Atherosclerosismentioning

confidence: 99%

Section: Initiation Of Atherosclerosismentioning

confidence: 99%

Section: Imaging As a Diagnostic Tool In Atherosclerosismentioning

confidence: 99%

Section: Imaging As a Diagnostic Tool In Atherosclerosismentioning

confidence: 99%

See 2 more Smart Citations

Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential

Márquez

Vorst

Maas

2021

JCM

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“…Even during development, TLS stroma presents a large degree of plasticity (Barone et al, 2016). Early anlagen mesenchyme can differentiate upon specific stimuli into diverse and highly specialized stroma, which then creates functional micro domains within the TLS (Asam et al, 2021). TLS non-vascular stroma is largely represented by fibroblastic reticular cells (FRC), a fine network of canaliculi forming fibroblasts that display unique functional properties, including the ability to support the dramatic anatomical remodelling required to adapt TLS to the influx occurring in response to antigen stimulation (Perez-Shibayama et al, 2019).…”

Section: Stromal Cell Composition and Architecture In Tertiary Lympho...mentioning

confidence: 99%

Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses

Rossi

Belmonte

Carnevale

et al. 2022

Front. Cell Dev. Biol.

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Tertiary lymphoid structures (TLS) are ectopic lymphoid organs that have been observed in chronic inflammatory conditions including cancer, where they are thought to exert a positive effect on prognosis. Both immune and non-immune cells participate in the genesis of TLS by establishing complex cross-talks requiring both soluble factors and cell-to-cell contact. Several immune cell types, including T follicular helper cells (Tfh), regulatory T cells (Tregs), and myeloid cells, may accumulate in TLS, possibly promoting or inhibiting their development. In this manuscript, we propose to review the available evidence regarding specific aspects of the TLS formation in solid cancers, including 1) the role of stromal cell composition and architecture in the recruitment of specific immune subpopulations and the formation of immune cell aggregates; 2) the contribution of the myeloid compartment (macrophages and neutrophils) to the development of antibody responses and the TLS formation; 3) the immunological and metabolic mechanisms dictating recruitment, expansion and plasticity of Tregs into T follicular regulatory cells, which are potentially sensitive to immunotherapeutic strategies directed to costimulatory receptors or checkpoint molecules.

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Modeling Structural Elements and Functional Responses to Lymphatic‐Delivered Cues in a Murine Lymph Node on a Chip

Mazzaglia,

Munir,

Lei

et al. 2024

Adv Healthcare Materials

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Lymph nodes (LNs) are organs of the immune system, critical for maintenance of homeostasis and initiation of immune responses, yet there are few models that accurately recapitulate LN functions in vitro. To tackle this issue, an engineered murine LN (eLN) was developed, replicating key cellular components of the mouse LN; incorporating primary murine lymphocytes, fibroblastic reticular cells (FRCs), and lymphatic endothelial cells (LECs). T and B cells compartments are incorporated within the eLN that mimic LN cortex and paracortex architectures. When challenged, the eLN elicits both robust inflammatory responses and antigen‐specific immune activation, showing that the system can differentiate between non‐specific and antigen‐specific responses and can be monitored in real‐time. Beyond immune responses, this model also enables interrogation of changes in stromal cells, thus permitting investigations of all LN cellular components in homeostasis and different disease settings, such as cancer. Here, we present how LN behavior can be influenced by murine melanoma‐derived factors. In conclusion, the eLN model presents a promising platform for in vitro study of LN biology that will enhance understanding of stromal and immune responses in the murine LN, and in doing so will enable development of novel therapeutic strategies to improve LN responses in disease.This article is protected by copyright. All rights reserved

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Stromal cells in tertiary lymphoid structures: Architects of autoimmunity

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 21 publications

References 110 publications

Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential

Key Chemokine Pathways in Atherosclerosis and Their Therapeutic Potential

Stromal and Immune Cell Dynamics in Tumor Associated Tertiary Lymphoid Structures and Anti-Tumor Immune Responses

Modeling Structural Elements and Functional Responses to Lymphatic‐Delivered Cues in a Murine Lymph Node on a Chip

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