Lymph Node Stromal Cells: Mapmakers of T Cell Immunity

Harlé, Guillaume; Kowalski, Camille; Garnier, Laure; Hugues, Stéphanie

doi:10.3390/ijms21207785

Cited by 15 publications

(16 citation statements)

References 124 publications

(156 reference statements)

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“…Recently, heterogeneity of stromal cells has been identified in murine LNs [43]. In fact, a number of subsets were identified, including marginal reticular cells, which produce CXCL13 which has a key role in B cell homing and migration towards follicles [44]. In the paracortex, two divergent subsets have been distinguished and express different levels of CCL19, a regulator of lymphocyte migration [43].…”

Section: Ln Organizationmentioning

confidence: 99%

The pre-metastatic niche in lymph nodes: formation and characteristics

Gillot

Baudin

Rouaud

et al. 2021

Cell. Mol. Life Sci.

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Lymph node metastasis is a crucial prognostic parameter in many different types of cancers and a gateway for further dissemination to distant organs. Prior to metastatic dissemination, the primary tumor prepares for the remodeling of the draining (sentinel) lymph node by secreting soluble factors or releasing extracellular vesicles that are transported by lymphatic vessels. These important changes occur before the appearance of the first metastatic cell and create what is known as a pre-metastatic niche giving rise to the subsequent survival and growth of metastatic cells. In this review, the lymph node structure, matrix composition and the emerging heterogeneity of cells forming it are described. Current knowledge of the major cellular and molecular processes associated with nodal pre-metastatic niche formation, including lymphangiogenesis, extracellular matrix remodeling, and immunosuppressive cell enlisting in lymph nodes are additionally summarized. Finally, future directions that research could possibly take and the clinical impact are discussed.

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Section: Ln Organizationmentioning

confidence: 99%

The pre-metastatic niche in lymph nodes: formation and characteristics

Gillot

Baudin

Rouaud

et al. 2021

Cell. Mol. Life Sci.

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“…The first one is from the lymph node stromal cells. Under normal physiologic conditions, these stromal cells are identified as structural supporters as well as regulators or recruiters of immune cells ( 33 , 120 , 121 ). Nevertheless, their possible epigenetic modulatory roles on the metastatic cancer cells should not be ignored.…”

Section: Discussionmentioning

confidence: 99%

“…Three main structural elements, including the cortex, paracortex, and medulla, help constitute the anatomical framework of the lymph node, and different types of immune cell populations own their main regional distribution. The cortex, consisting of the follicle, the interfollicular zone, and the subcapsular sinus, is the main resident area for B cell and dendritic cells, which regulated the process of antigen presentation and antibody production, while the paracortex is mainly distributed with T cells and the medulla is covered with macrophages ( 32 , 33 ).…”

Section: Complexity and Heterogeneity Of The Lymph Node Microenvironmentmentioning

confidence: 99%

“…Generally, immune cells are the “flesh” of the lymph node and the stromal cells are the “skeleton.” Functionally, lymph node stromal cells not only help form the architecture of the lymph node but also play important roles in regulating the normal function of those immune cells mainly by releasing cytokines such as CCL19, CCL21, and IL17 ( 33 , 34 ). Similar with previously mentioned immune cells, lymph node stromal cells also possess strong heterogeneity and regional distribution difference.…”

Section: Complexity and Heterogeneity Of The Lymph Node Microenvironmentmentioning

confidence: 99%

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The Lymph Node Microenvironment May Invigorate Cancer Cells With Enhanced Metastatic Capacities

Liu

Zhao

et al. 2022

Front. Oncol.

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Cancer metastasis, a typical malignant biological behavior involving the distant migration of tumor cells from the primary site to other organs, contributed majorly to cancer-related deaths of patients. Although constant efforts have been paid by researchers to elucidate the mechanisms of cancer metastasis, we are still far away from the definite answer. Recently, emerging evidence demonstrated that cancer metastasis is a continuous coevolutionary process mediated by the interactions between tumor cells and the host organ microenvironment, and epigenetic reprogramming of metastatic cancer cells may confer them with stronger metastatic capacities. The lymph node served as the first metastatic niche for many types of cancer, and the appearance of lymph node metastasis predicted poor prognosis. Importantly, multiple immune cells and stromal cells station and linger in the lymph nodes, which constitutes the complexity of the lymph node microenvironment. The active cross talk between cancer cells and immune cells could happen unceasingly within the metastatic environment of lymph nodes. Of note, diverse immune cells have been found to participate in the formation of malignant properties of tumor, including stemness and immune escape. Based on these available evidence and data, we hypothesize that the metastatic microenvironment of lymph nodes could drive cancer cells to metastasize to further organs through epigenetic mechanisms.

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“…This may suggest that these DCs are involved in sustaining inflammation during established RA, or that other DC subsets or other antigen presenting cells (APCs) are responsible for the initial break in tolerance. LNSC provide the structural integrity and framework for the important compartmentalization of lymphocytes within the LN (30). In recent years, mouse LNSC have been implicated more prominently in immune cell tolerance as they are able to delete self-reactive CD8 + T cells through PTA expression on major histocompatibility complex (MHC) I and on MHC II in the context of CD4 + T cells (27,28,31,32).…”

Section: Ln Studies Reveal Immune Cell Activation During the Earliest...mentioning

confidence: 99%

Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

2022

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Rheumatoid arthritis (RA) is a chronic autoimmune disease of unknown etiology characterized by inflammation of the peripheral synovial joints leading to pannus formation and bone destruction. Rheumatoid Factor (RF) and anti-citrullinated protein antibodies (ACPA) are present years before clinical manifestations and are indicative of a break in tolerance that precedes chronic inflammation. The majority of studies investigating disease pathogenesis focus on the synovial joint as target site of inflammation while few studies explore the initial break in peripheral tolerance which occurs within secondary lymphoid organs such as lymph nodes. If explored during the earliest phases of RA, lymph node research may provide innovative drug targets for disease modulation or prevention. RA research largely centers on the role and origin of lymphocytes, such as pro-inflammatory T cells and macrophages that infiltrate the joint, as well as growing efforts to determine the role of stromal cells within the synovium. It is therefore important to explore these cell types also within the lymph node as a number of mouse studies suggest a prominent immunomodulatory role for lymph node stromal cells. Synovium and proximal peripheral lymph nodes should be investigated in conjunction with one another to gain understanding of the immunological processes driving RA progression from systemic autoimmunity toward synovial inflammation. This perspective seeks to provide an overview of current literature concerning the immunological changes present within lymph nodes and synovium during early RA. It will also propose areas that warrant further exploration with the aim to uncover novel targets to prevent disease progression.

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Lymph Node Stromal Cells: Mapmakers of T Cell Immunity

Cited by 15 publications

References 124 publications

The pre-metastatic niche in lymph nodes: formation and characteristics

The pre-metastatic niche in lymph nodes: formation and characteristics

The Lymph Node Microenvironment May Invigorate Cancer Cells With Enhanced Metastatic Capacities

Bridging Insights From Lymph Node and Synovium Studies in Early Rheumatoid Arthritis

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