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Dysregulated gene expression in Autoimmunity and Inflammation
Dysregulated gene expression in Autoimmunity and Inflammation
Dr.V.Malathi
Genetics and environmental factors are implicated in the pathogenesis of many autoimmune diseases. Increasing evidence has shown that dysregulated epigenetic modifications are involved in pathogenesis of several autoimmune diseases.
SLE is a multi-organ involved autoimmune disease in which the immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs. It can affect the joints, skin, brain, lungs, kidneys, and blood vessels. SLE is characterized by aberrant immune cells, such as dendritic cells, B and T lymphocytes. Increasing evidence , have reported that DNA methylation plays a critical role in immune cells hyper-activation in lupus conditions. Genomic DNA in lupus CD4+ T cells has been found to show DNA hypomethylation. DNA hypomethylation is also reported in Lupus B cells.
Aberrant Histone Modifications is also contribute to Lupus. Lupus CD4+ T cells show global histone H3 and H4 hypoacetylation. Abnormal histone modifications have been found in the promoter region of TNFSF7 in T cells. This results in overexpression of CD70. This in turn might be the one cause of auto-reactivity of T cells. Histone hyperacetylation has been shown to be a cause for an increased serum level of TNF-α and an enhanced maturation status of monocytes from lupus patients. miRNAs are also involved in the aberrant B cell expression and functions. Lupus B cells shows increased levels of miR-30a
Psoriasis
is a chronic inflammatory autoimmune skin disease. It is characterized by hyper proliferation of keratinocytes and dysregulated T cells, especially Th17 cells. Epigenetic regulations on immune cells also attributing to psoriasis pathogenesis. Aberrant DNA methylation pattern has also been revealed in CD4+ T cells from psoriatic patients, indicating the role of epigenetic regulations.
RA is an autoreactive immune cell-mediated inflammation which primarily affects joints. Autoreactive immune cells and synovial fibroblasts play an important role in the pathogenesis of RA. Increasing evidence has shown that DNA methylation contributes to the pathogenesis of RA. Global DNA hypomethylation is also found in T cells from RA patients
SSc is a relatively rare disease which is characterized by damages of connective tissues mediated by autoreactive immune cells. Its etiopathogenesis remains unclear. Abnormal epigenetic modifications have been shown in SSc. Dysregulated DNA methylation is indicated in Systemic Sclerosis.
Multi-organ involved auto immune disease causing inflammation and tissue damage in the affected organs .
Chronic inflammatory autoimmune skin disease
Auto reactive immune cell mediated inflammatory condition primarily affecting the joints
Disease characterized by autoimmune cells mediated damage of the connective tissue