{"id":782,"date":"2023-04-03T10:09:33","date_gmt":"2023-04-03T10:09:33","guid":{"rendered":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/?post_type=chapter&p=782"},"modified":"2023-04-06T15:40:43","modified_gmt":"2023-04-06T15:40:43","slug":"dysregulated-gene-expression-in-autoimmunity-and-inflammation","status":"publish","type":"chapter","link":"https:\/\/pressbooks.justwrite.in\/understanding-gene-regulation\/chapter\/dysregulated-gene-expression-in-autoimmunity-and-inflammation\/","title":{"raw":"Dysregulated gene expression in Autoimmunity and Inflammation","rendered":"Dysregulated gene expression in Autoimmunity and Inflammation"},"content":{"raw":"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.<\/span>\r\n

[pb_glossary id=\"958\"]Systemic Lupus Erythematosus (SLE)[\/pb_glossary]<\/span><\/h1>\r\nSLE is a multi-organ involved autoimmune disease\u00a0<\/span> 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 <\/span>is characterized by aberrant immune cells, such as dendritic cells, B and T lymphocytes.\u00a0 Increasing evidence , have reported that DNA methylation plays a critical role in immune cells hyper-activation\u00a0 in lupus conditions<\/span>. Genomic DNA in lupus CD4+<\/sup> T cells\u00a0 has been found to show DNA hypomethylation. DNA hypomethylation is also reported in Lupus B cells.<\/span>\r\n\r\nAberrant Histone Modifications is also contribute to Lupus.\u00a0Lupus CD4+<\/sup>\u00a0<\/span>T cells show global histone H3 and H4 hypoacetylation. Abnormal histone modifications have been found in the promoter region of\u00a0<\/span>TNFSF7<\/em>\u00a0<\/span>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-\u03b1 and an enhanced maturation status of monocytes from lupus patients. <\/span>\u00a0miRNAs are also involved in the aberrant B cell expression and functions. Lupus B cells shows increased levels of miR-30a<\/span>\r\n

Psoriasis<\/h2>\r\n[pb_glossary id=\"960\"]Psoriasis [\/pb_glossary]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+<\/sup> T cells from psoriatic patients, indicating\u00a0 the role of epigenetic regulations.<\/span>\r\n

[pb_glossary id=\"962\"]Rheumatoid Arthritis\u00a0 (RA)[\/pb_glossary]<\/h2>\r\n\u00a0RA 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<\/span>\r\n

[pb_glossary id=\"964\"]Systemic Sclerosis (SSc)\u00a0[\/pb_glossary]<\/strong><\/h2>\r\n

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.<\/p>\r\n\r\n

\r\n\r\n \r\n\r\n<\/div>","rendered":"

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.<\/span><\/p>\n

Systemic Lupus Erythematosus (SLE)<\/a><\/span><\/h1>\n

SLE is a multi-organ involved autoimmune disease\u00a0<\/span> 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 <\/span>is characterized by aberrant immune cells, such as dendritic cells, B and T lymphocytes.\u00a0 Increasing evidence , have reported that DNA methylation plays a critical role in immune cells hyper-activation\u00a0 in lupus conditions<\/span>. Genomic DNA in lupus CD4+<\/sup> T cells\u00a0 has been found to show DNA hypomethylation. DNA hypomethylation is also reported in Lupus B cells.<\/span><\/p>\n

Aberrant Histone Modifications is also contribute to Lupus.\u00a0Lupus CD4+<\/sup>\u00a0<\/span>T cells show global histone H3 and H4 hypoacetylation. Abnormal histone modifications have been found in the promoter region of\u00a0<\/span>TNFSF7<\/em>\u00a0<\/span>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-\u03b1 and an enhanced maturation status of monocytes from lupus patients. <\/span>\u00a0miRNAs are also involved in the aberrant B cell expression and functions. Lupus B cells shows increased levels of miR-30a<\/span><\/p>\n

Psoriasis<\/h2>\n

Psoriasis <\/a>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+<\/sup> T cells from psoriatic patients, indicating\u00a0 the role of epigenetic regulations.<\/span><\/p>\n

Rheumatoid Arthritis\u00a0 (RA)<\/a><\/h2>\n

\u00a0RA 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<\/span><\/p>\n

Systemic Sclerosis (SSc)\u00a0<\/a><\/strong><\/h2>\n

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.<\/p>\n

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