A prominent role for mucosal cystine/cysteine metabolism in intestinal immunoregulation
BACKGROUND & AIMS: T-cell receptor reactivity of intestinal lamina propria T cells (LP-T) critically depends on the capacity of local accessory cells to secrete cysteine. For T cells, cysteine is the limiting precursor for glutathione synthesis, a prerequisite for antigen-dependent proliferation...
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| Main Authors: | , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2008
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| In: |
Gastroenterology
Year: 2008, Volume: 134, Issue: 1, Pages: 179-191 |
| ISSN: | 1528-0012 |
| DOI: | 10.1053/j.gastro.2007.11.001 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: http://dx.doi.org/10.1053/j.gastro.2007.11.001 Verlag, lizenzpflichtig, Volltext: https://linkinghub.elsevier.com/retrieve/pii/S0016-5085(07)01991-9 
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| Author Notes: | Bernd Sido, Felix Lasitschka, Thomas Giese, Nikolaus Gassler, Benjamin Funke, Jutta Schröder-Braunstein, Ulf Brunnemer, Stefan C. Meuer, and Frank Autschbach |
| Summary: | BACKGROUND & AIMS: T-cell receptor reactivity of intestinal lamina propria T cells (LP-T) critically depends on the capacity of local accessory cells to secrete cysteine. For T cells, cysteine is the limiting precursor for glutathione synthesis, a prerequisite for antigen-dependent proliferation. We aimed to determine the role of the redoxactive microenvironment for hyporeactivity of LP-T in normal human gut vs hyperreactivity of LP-T in inflammatory bowel disease. METHODS: Parameters relevant to cysteine production, determined as acid-soluble thiol, by intestinal lamina propria macrophages (LP-MO) vs peripheral blood monocytes were investigated (L-[(35)S]cystine uptake via system x(c)(-), messenger RNA, and protein expression of the cystine transporter subunit xCT). Glutathione levels in LP-T and peripheral blood T cells were analyzed both spectrophotometrically and by immunofluorescent staining in situ and in vitro. RESULTS: LP-MO from normal gut, unlike peripheral blood monocytes, are unable to take up cystine, which is due to a deficient expression of the transporter xCT in situ and in vitro. As a consequence, LP-MO do not secrete cysteine. The glutathione content in LP-T from normal gut is <50% of that in autologous peripheral blood T cells. In contrast, in inflammatory bowel disease, CD14(+)CD68(+) LP-MO express xCT and secrete substantial amounts of cysteine upon stimulation, which results in high glutathione levels and full T-cell receptor reactivity in LP-T. CONCLUSIONS: The antioxidative microenvironment of LP-T in inflammatory bowel disease and the prooxidative microenvironment in normal gut explain the differential T-cell receptor reactivities. |
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| Item Description: | Gesehen am 14.06.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0012 |
| DOI: | 10.1053/j.gastro.2007.11.001 |