| Genome-wide identification of novel genes involved in early Th1 and Th2 cell differentiation. | |
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MedLine Citation:
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PMID: 17339462 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Th cell subtypes, Th1 and Th2, are involved in the pathogenesis or progression of many immune-mediated diseases, such as type 1 diabetes and asthma, respectively. Defining the molecular networks and factors that direct Th1 and Th2 cell differentiation will help to understand the pathogenic mechanisms causing these diseases. Some of the key factors regulating this differentiation have been identified, however, they alone do not explain the process in detail. To identify novel factors directing the early differentiation, we have studied the transcriptomes of human Th1 and Th2 cells after 2, 6, and 48 h of polarization at the genome scale. Based on our current and previous studies, 288 genes or expressed sequence tags, representing approximately 1-1.5% of the human genome, are regulated in the process during the first 2 days. These transcriptional profiles revealed genes coding for components of certain pathways, such as RAS oncogene family and G protein-coupled receptor signaling, to be differentially regulated during the early Th1 and Th2 cell differentiation. Importantly, numerous novel genes with unknown functions were identified. By using short-hairpin RNA knockdown, we show that a subset of these genes is regulated by IL-4 through STAT6 signaling. Furthermore, we demonstrate that one of the IL-4 regulated genes, NDFIP2, promotes IFN-gamma production by the polarized human Th1 lymphocytes. Among the novel genes identified, there may be many factors that play a crucial role in the regulation of the differentiation process together with the previously known factors and are potential targets for developing therapeutics to modulate Th1 and Th2 responses. |
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Authors:
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Riikka J Lund; Maritta Löytömäki; Tiina Naumanen; Craig Dixon; Zhi Chen; Helena Ahlfors; Soile Tuomela; Johanna Tahvanainen; Joonas Scheinin; Tiina Henttinen; Omid Rasool; Riitta Lahesmaa |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 178 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2007 Mar |
Date Detail:
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Created Date: 2007-03-06 Completed Date: 2007-05-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 3648-60 Citation Subset: AIM; IM |
Affiliation:
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Centre for Biotechnology, University of Turku and Abo Akademi University, FIN-20521 Turku, Finland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Differentiation
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physiology* Cells, Cultured Gene Expression Profiling Gene Expression Regulation / physiology* Genome, Human / physiology* Humans Interleukin-4 / immunology Oligonucleotide Array Sequence Analysis Reverse Transcriptase Polymerase Chain Reaction STAT6 Transcription Factor / immunology Signal Transduction / immunology Th1 Cells / physiology* Th2 Cells / physiology* Time Factors Transcription, Genetic / physiology* |
| Chemical | |
Reg. No./Substance:
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0/IL4 protein, human; 0/STAT6 Transcription Factor; 0/STAT6 protein, human; 207137-56-2/Interleukin-4 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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