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

Basic, Marijana; Peppermüller, Pia Pascale; Bolsega, Silvia; Bleich, André; Bornemann, Melanie; Bode, Ulrike; Büettner, Manuela

doi:10.3389/fimmu.2020.549473

Cited by 7 publications

(6 citation statements)

References 40 publications

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“…Limited data are available on MLN and PPs in humoral responses, as well as on the implication of lymph node stroma in IBD pathophysiology [67,68,71,73,83,84,90,91,94]. While lymphatic obstruction by granulomas in MLNs and lymphatic vessels correlates with disease severity [2,10,[123][124][125], data on the role of lymphangiogenesis in disease activity are contradictory [116,117,[120][121][122].…”

Section: Discussionmentioning

confidence: 99%

“…In a murine model of intestinal autoimmunity, MLN stromal cells could partially promote T-cell tolerance by reducing only the CD8 + autoreactive T-cells [89]. Additionally, in mice with colitis, peripheral LN stromal cells were more tolerogenic and ameliorated the disease, compared to MLN stromal cells, which demonstrated a more proinflammatory profile [90].…”

Section: The Involvement Of the Lymphatic System Stromal Components I...mentioning

confidence: 99%

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The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Nikolakis

Voogd

Pruijt

et al. 2022

IJMS

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Although the number of therapeutic options for the treatment of inflammatory bowel disease (IBD) has increased in recent years, patients suffer from decreased quality of life due to non-response or loss of response to the currently available treatments. An increased understanding of this disease’s etiology could provide novel insights for treatment strategies in IBD. Lymphatic system components are generally linked to immune responses and presumably related to inflammatory diseases pathophysiology. This review aims to summarize findings on immune-mediated mechanisms in lymphoid tissues linked with IBD pathogenesis and (potential) novel treatments. Enhanced innate and adaptive immune responses were observed in mesenteric lymph nodes (MLNs) and other lymphoid structures, such as Peyer’s patches, in patients with IBD and in animal models. Furthermore, the phenomenon of lymphatic obstruction in the form of granulomas in MLNs and lymphatic vessels correlates with disease activity. There is also evidence that abnormalities in the lymphatic stromal components and lymph node microbiome are common in IBD and could be exploited therapeutically. Finally, novel agents targeting lymphocyte trafficking have been added to the treatment armamentarium in the field of IBD. Overall, gut-associated lymphoid tissue plays a key role in IBD immunopathogenesis, which could offer novel therapeutic targets.

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Section: Discussionmentioning

confidence: 99%

Section: The Involvement Of the Lymphatic System Stromal Components I...mentioning

confidence: 99%

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Nikolakis

Voogd

Pruijt

et al. 2022

IJMS

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“…In the gut mucosa, immune cells can be found in organized secondary lymphoid structures, collectively known as gut-associated lymphoid tissue, as well as in intestinal tissue draining mesenteric lymph nodes (mLN), embedded between surface epithelial cells, and within the underlying connective tissue [1]. Research has shown that immune cells in secondary lymph nodes play an important role in the progression of IBD [23]. Therefore, we further analyzed the changes in the proportion of immune cells in the mLN of each group by flow cytometry.…”

Section: Ifn-γ-and Kyna-primed Hadscs Promoted Polarization Of M2 Mac...mentioning

confidence: 99%

Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn’s colon fibrosis is improved by IFN-γ and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling

Zhang

et al. 2022

Stem Cell Res Ther

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Background Inflammatory bowel diseases (IBD) are chronic relapsing–remitting inflammatory diseases of the gastrointestinal tract that are typically categorized into two subtypes: Crohn's disease (CD) and ulcerative colitis (UC). Although MSCs therapy has achieved encouraging outcomes in IBD therapy, objective responses are limited in colon fibrosis stenosis owing to the complicated microenvironment of CD and MSCs heterogeneity of quality. Here, we chose IFN-γ and kynurenic acid (KYNA) to overcome the low response and heterogeneity of human adipose-derived MSCs (hADSCs) to treat IBD and expand the therapeutic effects based on the excellent ability of IFN-γ and KYNA to promote indoleamine 2,3-dioxygenase-1 (IDO-1) signaling, providing a potential protocol to treat IBD and fibrosis disease. Methods hADSCs were isolated, cultured, and identified from human abdominal adipose tissue. The CD pathology-like acute colitis and chronic colon fibrosis rat model was induced by 2,4,6-trinitrobenzen sulfonic acid (TNBS). hADSCs were pretreated in vitro with IFN-γ and KYNA and then were transplanted intravenously at day 1 and 3 of TNBS administration in colitis along with at day 1, 15, and 29 of TNBS administration in chronic colonic fibrosis. Therapeutic efficacy was evaluated by body weights, disease activity index, pathological staining, real-time PCR, Western blot, and flow cytometry. For knockout of IDO-1, hADSCs were transfected with IDO-1-targeting small gRNA carried on a CRISPR-Cas9-lentivirus vector. Results hADSCs treated with IFN-γ and KYNA significantly upregulated the expression and secretion of IDO-1, which has effectively ameliorated CD pathology-like colitis injury and fibrosis. Notably, the ability of hADSCs with IDO-1 knockout to treat colitis was significantly impaired and diminished the protective effects of the primed hADSCs with IFN-γ and KYNA. Conclusion Inflammatory cytokines IFN-γ- and KYNA-treated hADSCs more effectively alleviate TNBS-induced colitis and colonic fibrosis through an IDO-1-dependent manner. Primed hADSCs are a promising new strategy to improve the therapeutic efficacy of MSCs and worth further research.

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“…Compared with healthy mammary epithelial cells, breast cancer cells also displayed upregulated surface CXCR4 and CCR7 receptors [92,93] (specific for CXCL12 and CCL19/CCL21, respectively) [94,95]. CXCL12, CCL19, CCL21, and CXCL16 are all expressed by LNSCs and are important for directing lymphocyte homing [94,96,97]; they might therefore also attract and coordinate cancer cell migration and invasion. Moreover, analysis of human breast cancer LNs has provided evidence that the reorganization of HEVs in pre-metastatic LNs is associated with aberrant secretion of CCL21 in perivascular FRCs compared with cancer-free LNs [98].…”

Section: In Cancer Lnscs Can Favor Immune Evasion and Metastasismentioning

confidence: 99%

Lymph node stromal cells: subsets and functions in health and disease

Grasso

Pierie

Mebius

et al. 2021

Trends in Immunology

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Lymph nodes (LNs) aid the interaction between lymphocytes and antigenpresenting cells, resulting in adequate and prolonged adaptive immune responses. LN stromal cells (LNSCs) are crucially involved in steering adaptive immune responses at different levels. Most knowledge on LNSCs has been obtained from mouse studies, and few studies indicate similarities with their human counterparts. Recent advances in single-cell technologies have revealed significant LNSC heterogeneity among different subsets with potential selective functions in immunity. This review provides an overview of current knowledge of LNSCs based on human and murine studies describing the role of these cells in health and disease. LNSCs as orchestrators of the immune systemLNs are specialized secondary lymphoid organs (SLOs) that are essential for the initiation of adaptive immunity. Most cells within LNs are lymphocytes that continuously enter the LN from the bloodstream. The afferent lymph transports antigens and antigen-presenting cells (APCs; see Glossary) to the LN, which creates an environment in which antigen-specific lymphocytes and APCs can optimally interact, resulting in adequate and prolonged immune responses [1]. The architecture of the LN is pivotal for its role in inducing humoral immune responses, and this is created and supported by LNSCs (Box 1) [2]. LNSCs create a 3D network that generates a backbone for immune cells to migrate on, and thus, during the time lymphocytes reside in the LN, they extensively interact with stromal cells. In addition to providing structural support, LNSCs also provide survival signals, nutrients, soluble factors, and antigens that are collectively required for immunosurveillance as well as for the generation and control of adaptive immune responses [3,4]. Therefore, understanding the immunobiology of LNSCs is key to comprehending specific aspects of the immune system more fully. The aim of this review is to provide an overview of the current state of knowledge about murine and human LNSC subsets and functions. We discuss recent findings regarding human and mouse LNSCs under homeostatic conditions, and describe their immunomodulatory capacities during autoimmunity, infection, and cancer. We anticipate that some of these findings may fuel further investigations into the field of LN biology and immune defense across species. HighlightsSingle-cell RNA sequencing has uncovered conspicuous heterogeneity in lymph node stromal cells (LNSCs) populations in mice and humans.Human and mouse LNSC subsets show similarities in their transcriptomic profiles and trajectory analyses.Each LNSC subset has its own specific function in regulating immune responses.Human LNSCs have the machinery to regulate peripheral tolerance, making them attractive targets for modulating tolerance induction and maintenance.LNSCs in mice and humans can suppress T cell proliferation during strong inflammatory stimuli. Different mechanisms are utilized to perform this function.LNSCs from patients with particular autoimmune diseases exhibit alte...

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

Cited by 7 publications

References 40 publications

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

Therapeutic efficacy of human adipose mesenchymal stem cells in Crohn’s colon fibrosis is improved by IFN-γ and kynurenic acid priming through indoleamine 2,3-dioxygenase-1 signaling

Lymph node stromal cells: subsets and functions in health and disease

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