Adaptation of Human CD4+ T Cells to Pathophysiological Hypoxia: A Transcriptome Analysis. Export

@article{citeulike:6071677, abstract = {OBJECTIVE: Inflamed tissues are usually characterized by low oxygen levels. We investigated whether pathophysiological hypoxia (pO2 < 1\%) as found in the rheumatoid synovium modulates the transcriptome of human CD4+ T cells. METHODS: We analyzed the extent to which hypoxia influences the transcriptome in the rheumatoid synovium according to a gene cluster reflecting adaptation to low oxygen levels. Hypoxia-inducible factor-1alpha (HIF-1alpha) was detected in the rheumatoid synovium using immunohistochemistry. Isolated human CD4+ T cells were exposed to hypoxia and analyzed using microarray analysis, quantitative polymerase chain reaction, and immunoblot detection. RESULTS: In rheumatoid arthritis (RA) synovial tissue samples, hypoxia modulates the transcription profile. This profile is similar, but not identical, to that found in isolated CD4+ T cells incubated under hypoxic conditions. We show that HIF-1alpha is expressed in synovial tissue samples and in hypoxic CD4+ cells; and that hypoxia directly affects differential gene expression in human T cells with up to 4.8\% modulation of the transcriptome. Functional genome analysis revealed substantial effects of hypoxia on immune response, transcriptional regulation, protein modification, cell growth and proliferation, and cell metabolism. CONCLUSION: Severe hypoxia, a feature of joint inflammation, considerably modulates the transcriptome of cells found in the rheumatoid synovium. Human CD4+ T cells adapt to hypoxic conditions mainly by HIF-1-driven effects on the transcriptome reflecting a profound influence on immune functions. Thus, hypoxia must be taken into account when therapeutically targeting inflammation.}, author = {Gaber, Timo and H\"{a}upl, Thomas and Sandig, Grit and Tykwinska, Karolina and Fangradt, Monique and Tschirschmann, Miriam and Hahne, Martin and Dziurla, Ren\'{e} and Erekul, Kerem and Lautenbach, Martin and Kolar, Paula and Burmester, Gerd-R\"{u}diger R. and Buttgereit, Frank}, citeulike-article-id = {6071677}, citeulike-linkout-0 = {http://dx.doi.org/10.3899/jrheum.090255}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19884271}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19884271}, day = {2}, doi = {10.3899/jrheum.090255}, issn = {0315-162X}, journal = {The Journal of rheumatology}, keywords = {a, adaptation, analysis, cd4, cells, human, hypoxia, of, pathophysiological, t, to, transcriptome}, month = {November}, posted-at = {2009-11-04 22:24:25}, priority = {2}, title = {Adaptation of Human CD4+ T Cells to Pathophysiological Hypoxia: A Transcriptome Analysis.}, url = {http://dx.doi.org/10.3899/jrheum.090255}, year = {2009} }

TY - JOUR ID - citeulike:6071677 L3 - citeulike-article-id:6071677 N2 - OBJECTIVE: Inflamed tissues are usually characterized by low oxygen levels. We investigated whether pathophysiological hypoxia (pO2 < 1%) as found in the rheumatoid synovium modulates the transcriptome of human CD4+ T cells. METHODS: We analyzed the extent to which hypoxia influences the transcriptome in the rheumatoid synovium according to a gene cluster reflecting adaptation to low oxygen levels. Hypoxia-inducible factor-1alpha (HIF-1alpha) was detected in the rheumatoid synovium using immunohistochemistry. Isolated human CD4+ T cells were exposed to hypoxia and analyzed using microarray analysis, quantitative polymerase chain reaction, and immunoblot detection. RESULTS: In rheumatoid arthritis (RA) synovial tissue samples, hypoxia modulates the transcription profile. This profile is similar, but not identical, to that found in isolated CD4+ T cells incubated under hypoxic conditions. We show that HIF-1alpha is expressed in synovial tissue samples and in hypoxic CD4+ cells; and that hypoxia directly affects differential gene expression in human T cells with up to 4.8% modulation of the transcriptome. Functional genome analysis revealed substantial effects of hypoxia on immune response, transcriptional regulation, protein modification, cell growth and proliferation, and cell metabolism. CONCLUSION: Severe hypoxia, a feature of joint inflammation, considerably modulates the transcriptome of cells found in the rheumatoid synovium. Human CD4+ T cells adapt to hypoxic conditions mainly by HIF-1-driven effects on the transcriptome reflecting a profound influence on immune functions. Thus, hypoxia must be taken into account when therapeutically targeting inflammation. JF - The Journal of rheumatology SN - 0315-162X TI - Adaptation of Human CD4+ T Cells to Pathophysiological Hypoxia: A Transcriptome Analysis. KW - a KW - adaptation KW - analysis KW - cd4 KW - cells KW - human KW - hypoxia KW - of KW - pathophysiological KW - t KW - to KW - transcriptome AU - Gaber, Timo AU - Häupl, Thomas AU - Sandig, Grit AU - Tykwinska, Karolina AU - Fangradt, Monique AU - Tschirschmann, Miriam AU - Hahne, Martin AU - Dziurla, René AU - Erekul, Kerem AU - Lautenbach, Martin AU - Kolar, Paula AU - Burmester, Gerd-Rüdiger AU - Buttgereit, Frank PY - 2009/11/02/ UR - http://dx.doi.org/10.3899/jrheum.090255 ER -