التفاصيل البيبلوغرافية
| العنوان: |
Reduced Expression of FOXP3 and Regulatory T-Cell Function in Severe Forms of Early-onset Autoimmune Enteropathy. |
| المؤلفون: |
Moes, Nicolette, Rieux–Laucat, Frédéric, Begue, Bernadette, Verdier, Julien, Neven, Bénédicte, Patey, Natacha, Torgerson, Troy T., Picard, Capucine, Stolzenberg, Marie–Claude, Ruemmele, Corinne, Rings, Edmond Hhm, Casanova, Jean–Laurent, Piloquet, Hugues, Biver, Armand, Breton, Anne, Ochs, Hans D., Hermine, Olivier, Fischer, Alain, Goulet, Olivier, Cerf–Bensussan, Nadine |
| المصدر: |
Gastroenterology (00165085); Sep2010, Vol. 139 Issue 3, p770-778, 9p |
| مصطلحات موضوعية: |
AUTOIMMUNE diseases, INTESTINAL diseases, GENE expression, T cell receptors, POLYMERASE chain reaction, TRANSCRIPTION factors, INTERLEUKINS, MESSENGER RNA |
| مستخلص: |
Background & Aims: Little is known about the pathophysiology of early onset forms of autoimmune enteropathy (AIE). AIE has been associated with mutations in FOXP3—a transcription factor that controls regulatory T-cell development and function. We analyzed the molecular basis of neonatal or early postnatal AIE using clinical, genetic, and functional immunological studies. Methods: Gastroenterological and immunological features were analyzed in 9 boys and 2 girls with AIE that began within the first 5 months of life. FOXP3 and IL2RA were genotyped in peripheral blood monocytes. FOXP3 messenger RNA and protein expression were analyzed using reverse-transcription polymerase chain reaction, flow cytometry, and confocal immunofluorescence of CD4+ T cells. Regulatory T-cell function (CD4+CD25+) was assayed in coculture systems. Results: AIE associated with extraintestinal autoimmunity was severe and life-threatening; all patients required total parenteral nutrition. Regulatory T cells from 7 patients had altered function and FOXP3 mutations that resulted in lost or reduced FOXP3 protein expression; 2 infants had reduced regulatory T-cell activity and reduced levels of FOXP3 protein, although we did not detect mutations in FOXP3 coding region, poly-A site, or promoter region (called FOXP3-dependent AIE). Two patients had a normal number of regulatory T cells that expressed normal levels of FOXP3 protein and normal regulatory activity in in vitro coculture assays (called FOXP3-independent AIE). No mutations in IL2RA were found. Conclusions: Most cases of AIE are associated with alterations in regulatory T-cell function; some, but not all, cases have mutations that affect FOXP3 expression levels. Further studies are needed to identify mechanisms of AIE pathogenesis. [ABSTRACT FROM AUTHOR] |
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