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Gorman, Claire; Leandro, Maria; Isenberg, David

doi:10.1186/ar1007

Cited by 46 publications

(6 citation statements)

References 30 publications

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“…Immunoglobulin deposition is a recognised feature of several chronic inflammatory disorders, such as rheumatoid arthritis and the active role of B-cells in autoimmune disease is evidenced by a decrease in disease severity following B-cell depletion in patients [ 24 ]. Immunoglobulin deposition and a B-cell role in disease is also proposed for several carcinomas, including breast and prostate cancer and was observed experimentally in the skin of human papillomavirus 16 (HPV16) transgenic mice [ 25 ].…”

Section: Resultsmentioning

confidence: 99%

Lymphocyte deficiency limits Epstein-Barr virus latent membrane protein 1 induced chronic inflammation and carcinogenic pathology in vivo

et al. 2011

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BackgroundThe importance of the malignant cell environment to its growth and survival is becoming increasingly apparent, with dynamic cross talk between the neoplastic cell, the leukocyte infiltrate and the stroma. Most cancers are accompanied by leukocyte infiltration which, contrary to an anticipated immuno-protective role, could be contributing to tumour development and cancer progression. Epstein-Barr virus (EBV) associated cancers, including nasopharyngeal carcinoma and Hodgkin's Disease, show a considerable leukocyte infiltration which surrounds the neoplastic cells, raising the questions as to what role these cells play in either restricting or supporting the tumour and what draws the cells into the tumour. In order to begin to address this we have studied a transgenic model of multistage carcinogenesis with epithelial expression of the EBV primary oncoprotein, latent membrane protein 1 (LMP1). LMP1 is expressed particularly in the skin, which develops a hyperplastic pathology soon after birth.ResultsThe pathology advances with time leading to erosive dermatitis which is inflamed with a mixed infiltrate involving activated CD8+ T-cells, CD4+ T-cells including CD4+/CD25+/FoxP3+ Treg cells, mast cells and neutrophils. Also significant dermal deposition of immunoglobulin-G (IgG) is observed as the pathology advances. Along with NF-kappaB activation, STAT3, a central factor in inflammation regulation, is activated in the transgenic tissue. Several inflammatory factors are subsequently upregulated, notably CD30 and its ligand CD153, also leukocyte trafficking factors including CXCL10, CXCL13, L-selectin and TGFβ1, and inflammatory cytokines including IL-1β, IL-3 and the murine IL-8 analogues CXCL1, CXCL2 and CXCL5-6, amongst others. The crucial role of mature T- and/or B-lymphocytes in the advancing pathology is demonstrated by their elimination, which precludes mast cell infiltration and limits the pathology to an early, benign stage.ConclusionsLMP1 can lead to the activation of several key factors mediating proliferation, angiogenesis and inflammation in vivo. With the initiation of an inflammatory programme, leukocyte recruitment follows which then itself contributes to the progressing pathology in these transgenic mice, with a pivotal role for B-and/or T-cells in the process. The model suggests a basis for the leukocyte infiltrate observed in EBV-associated cancer and its supporting role, as well as potential points for therapeutic intervention.

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Section: Resultsmentioning

confidence: 99%

Lymphocyte deficiency limits Epstein-Barr virus latent membrane protein 1 induced chronic inflammation and carcinogenic pathology in vivo

et al. 2011

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“…Several reports have highlighted the association between failure to respond to B cell-depleting therapies and the persistence of TLS in the tissue of patients with autoimmune conditions (39–47). These observations establish a pathogenic role for TLS and their local microenvironment to sustain pathology.…”

Section: Discussionmentioning

confidence: 99%

Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology

Nayar

Campos

Smith

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

138

203

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Resident fibroblasts at sites of infection, chronic inflammation, or cancer undergo phenotypic and functional changes to support leukocyte migration and, in some cases, aggregation into tertiary lymphoid structures (TLS). The molecular programming that shapes these changes and the functional requirements of this population in TLS development are unclear. Here, we demonstrate that external triggers at mucosal sites are able to induce the progressive differentiation of a population of podoplanin (pdpn)-positive stromal cells into a network of immunofibroblasts that are able to support the earliest phases of TLS establishment. This program of events, that precedes lymphocyte infiltration in the tissue, is mediated by paracrine and autocrine signals mainly regulated by IL13. This initial fibroblast network is expanded and stabilized, once lymphocytes are recruited, by the local production of the cytokines IL22 and lymphotoxin. Interfering with this regulated program of events or depleting the immunofibroblasts in vivo results in abrogation of local pathology, demonstrating the functional role of immunofibroblasts in supporting TLS maintenance in the tissue and suggesting novel therapeutic targets in TLS-associated diseases.

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“…Similar to CD44, higher level of COMP is found in RA patients compared to OA patients [ 11 ]. When the COMP level was compared within the category of RA patients with slow and rapid progression of joint damage, COMP is distinguishably higher in those with severed joint destruction [ 80 ]. This characteristic of COMP makes it useful for identifying patients that are at high risk for joint destruction and can be potently used as a biomarker to monitor cartilage degradation [ 79 ].…”

Section: Role Of Immune-related Secretory Molecules In Rheumatoid mentioning

confidence: 99%

“…These RA-specific targets comprise of immune or non-immune cells, cellular receptors and soluble factors. The cell-based therapies include B-cells and T-cell depletion [ 80 ]. The RA therapies target cellular receptors such as IL-6 receptors [ 81 ] and CD20 [ 82 ] as well as membrane-bound and soluble factors (mainly cytokines) such as GM-CSF, BAFF and TNF-α [ 83 , 84 ].…”

Section: Targeting Immunological Components For Rheumatoid Arthritmentioning

confidence: 99%

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

Yap

Tee

Wong

et al. 2018

Cells

355

242

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Rheumatoid arthritis (RA) is a chronic, autoimmune, systemic, inflammatory disorder that affects synovial joints, both small and large joints, in a symmetric pattern. This disorder usually does not directly cause death but significantly reduces the quality of life and life expectancy of patients if left untreated. There is no cure for RA but, patients are usually on long-term disease modifying anti-rheumatic drugs (DMARDs) to suppress the joint inflammation, to minimize joint damage, to preserve joint function, and to keep the disease in remission. RA is strongly associated with various immune cells and each of the cell type contributes differently to the disease pathogenesis. Several types of immunomodulatory molecules mainly cytokines secreted from immune cells mediate pathogenesis of RA, hence complicating the disease treatment and management. There are various treatments for RA depending on the severity of the disease and more importantly, the patient’s response towards the given drugs. Early diagnosis of RA and treatment with (DMARDs) are known to significantly improve the treatment outcome of patients. Sensitive biomarkers are crucial in early detection of disease as well as to monitor the disease activity and progress. This review aims to discuss the pathogenic role of various immune cells and immunological molecules in RA. This review also highlights the importance of understanding the immune cells in treating RA and in exploring novel biomarkers.

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Untitled

Cited by 46 publications

References 30 publications

Lymphocyte deficiency limits Epstein-Barr virus latent membrane protein 1 induced chronic inflammation and carcinogenic pathology in vivo

Lymphocyte deficiency limits Epstein-Barr virus latent membrane protein 1 induced chronic inflammation and carcinogenic pathology in vivo

Immunofibroblasts are pivotal drivers of tertiary lymphoid structure formation and local pathology

Pathogenic Role of Immune Cells in Rheumatoid Arthritis: Implications in Clinical Treatment and Biomarker Development

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