Dataset Information

Lymphoid neogenesis and immune infiltration in aged liver.

ABSTRACT: Immune dysregulation and inflammation play a major role in the pathology of age-related disorders. In an earlier study, the microarray data from our laboratory indicated an increase in inflammation-related gene expression in the liver with age. We further investigated immune-related changes in the aged liver and found that the levels of inflammatory cytokines, chemokines, and inflammatory genes were higher in aged animals. Immunohistochemical studies showed that immune cells formed clusters or foci in the livers of old mice, preferentially near the perivascular regions. Further analysis revealed an enrichment of macrophages, T cells, B cells, natural killer cells, and neutrophils in old liver. Characterization of the immune clusters showed the presence of shared markers of tertiary lymphoid neogenesis. Levels of lymph node homing cytokines were elevated. Expression of immunoglobulin and recombinase gene transcripts was also higher, indicating the presence of ectopic lymphoid structures in the aged liver.Aged liver exhibits a marked inflammatory status accompanied by increased immune cell infiltration. Inflammation and ectopic lymphoid structures have previously been shown to be associated with carcinogenesis, a condition that becomes more prevalent with age. Thus, further study of inflammation-related changes in the microenvironment of the aged liver could provide insights into these disorders.

SUBMITTER: Singh P

PROVIDER: S-EPMC2859446 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Lymphoid neogenesis and immune infiltration in aged liver.

Singh Pallavi P Coskun Zeynep Z ZZ Goode Catriona C Dean Adam A Thompson-Snipes LuAnn L Darlington Gretchen G

Hepatology (Baltimore, Md.) 20080501 5

<h4>Unlabelled</h4>Immune dysregulation and inflammation play a major role in the pathology of age-related disorders. In an earlier study, the microarray data from our laboratory indicated an increase in inflammation-related gene expression in the liver with age. We further investigated immune-related changes in the aged liver and found that the levels of inflammatory cytokines, chemokines, and inflammatory genes were higher in aged animals. Immunohistochemical studies showed that immune cells f ...[more]

PMID: 18395842

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Project description:BACKGROUND: Ectopic lymphoid neogenesis (LN) occurs in rheumatoid synovium, where it is thought to drive local antigen-dependent B cell development and autoantibody production. This process involves the expression of specific homing chemokines and the development of high endothelial venules (HEV). OBJECTIVE: To investigate whether these mechanisms occur in psoriatic arthritis (PsA) synovium, where autoantibodies have not been described and the organisation and function of B cells is not clear, and to analyse their clinical correlates. METHODS: Arthroscopic synovial biopsy specimens from patients with PsA before and after tumour necrosis factor alpha blockade were characterised by immunohistochemical analysis for T/B cell segregation, peripheral lymph node addressin (PNAd)-positive HEV, and the expression of CXCL13, CCL21 and CXCL12 chemokines in relation to the size of lymphoid aggregates. RESULTS: Lymphoid aggregates of variable sizes were observed in 25 of 27 PsA synovial tissues. T/B cell segregation was often observed, and was correlated with the size of lymphoid aggregates. A close relationship between the presence of large and highly organised aggregates, the development of PNAd+ HEV, and the expression of CXCL13 and CCL21 was found. Large organised aggregates with all LN features were found in 13 of 27 tissues. LN in PsA synovitis was not related to the duration, pattern or severity of the disease. The synovial LN pattern remained stable over time in persistent synovitis, but a complete response to treatment was associated with a regression of the LN features. CONCLUSIONS: LN occurs frequently in inflamed PsA synovial tissues. Highly organised follicles display the characteristic features of PNAd+ HEV and CXCL13 and CCL21 expression, demonstrating that the microanatomical bases for germinal centre formation are present in PsA. The regression of LN on effective treatment indicates that the pathogenic and clinical relevance of these structures in PsA merits further investigation.

Dataset Information

Lymphoid neogenesis and immune infiltration in aged liver.

Publications

Lymphoid neogenesis and immune infiltration in aged liver.

Similar Datasets

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