A prominent role for mucosal cystine/cysteine metabolism in intestinal immunoregulation - PubMed (original) (raw)
A prominent role for mucosal cystine/cysteine metabolism in intestinal immunoregulation
Bernd Sido et al. Gastroenterology. 2008 Jan.
Abstract
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.
Similar articles
- Thiol-mediated redox regulation of intestinal lamina propria T lymphocytes.
Sido B, Braunstein J, Breitkreutz R, Herfarth C, Meuer SC. Sido B, et al. J Exp Med. 2000 Sep 18;192(6):907-12. doi: 10.1084/jem.192.6.907. J Exp Med. 2000. PMID: 10993921 Free PMC article. - A functional role for interleukin-21 in promoting the synthesis of the T-cell chemoattractant, MIP-3alpha, by gut epithelial cells.
Caruso R, Fina D, Peluso I, Stolfi C, Fantini MC, Gioia V, Caprioli F, Del Vecchio Blanco G, Paoluzi OA, Macdonald TT, Pallone F, Monteleone G. Caruso R, et al. Gastroenterology. 2007 Jan;132(1):166-75. doi: 10.1053/j.gastro.2006.09.053. Epub 2006 Oct 1. Gastroenterology. 2007. PMID: 17241869 - Two-photon analysis of calcium signals in T lymphocytes of intact lamina propria from human intestine.
Tutsch E, Griesemer D, Schwarz A, Stallmach A, Hoth M. Tutsch E, et al. Eur J Immunol. 2004 Dec;34(12):3477-84. doi: 10.1002/eji.200425265. Eur J Immunol. 2004. PMID: 15495161 - Generation of gut-homing T cells and their localization to the small intestinal mucosa.
Johansson-Lindbom B, Agace WW. Johansson-Lindbom B, et al. Immunol Rev. 2007 Feb;215:226-42. doi: 10.1111/j.1600-065X.2006.00482.x. Immunol Rev. 2007. PMID: 17291292 Review. - Repertoire of the alpha beta T-cell receptor in the intestine.
Probert CS, Saubermann LJ, Balk S, Blumberg RS. Probert CS, et al. Immunol Rev. 2007 Feb;215:215-25. doi: 10.1111/j.1600-065X.2006.00480.x. Immunol Rev. 2007. PMID: 17291291 Review.
Cited by
- Immunoregulation through membrane proteins modified by reducing conditions induced by immune reactions.
Stegmann M, Metcalfe C, Barclay AN. Stegmann M, et al. Eur J Immunol. 2013 Jan;43(1):15-21. doi: 10.1002/eji.201242849. Eur J Immunol. 2013. PMID: 23233323 Free PMC article. Review. - Immunomodulation of human intestinal T cells by the synthetic CD80 antagonist RhuDex®.
Heninger AK, Wentrup S, Al-Saeedi M, Schiessling S, Giese T, Wartha F, Meuer S, Schröder-Braunstein J. Heninger AK, et al. Immun Inflamm Dis. 2014 Nov;2(3):166-80. doi: 10.1002/iid3.34. Epub 2014 Nov 3. Immun Inflamm Dis. 2014. PMID: 25505551 Free PMC article. - PET Imaging of System xC - in Immune Cells for Assessment of Disease Activity in Mice and Patients with Inflammatory Bowel Disease.
Seo M, Kim Y, Ye BD, Park SH, Kim SY, Jung JH, Hwang SW, Chae SY, Lee DY, Lee SJ, Oh SJ, Kim J, Kim JY, Na SJ, Kim M, Kim SY, Koglin N, Stephens AW, Kweon MN, Moon DH. Seo M, et al. J Nucl Med. 2022 Oct;63(10):1586-1591. doi: 10.2967/jnumed.121.263289. Epub 2022 Jan 27. J Nucl Med. 2022. PMID: 35086893 Free PMC article. - Amino acids and immune response: a role for cysteine, glutamine, phenylalanine, tryptophan and arginine in T-cell function and cancer?
Sikalidis AK. Sikalidis AK. Pathol Oncol Res. 2015 Jan;21(1):9-17. doi: 10.1007/s12253-014-9860-0. Epub 2014 Oct 29. Pathol Oncol Res. 2015. PMID: 25351939 Review. - Intestinal redox biology and oxidative stress.
Circu ML, Aw TY. Circu ML, et al. Semin Cell Dev Biol. 2012 Sep;23(7):729-37. doi: 10.1016/j.semcdb.2012.03.014. Epub 2012 Mar 30. Semin Cell Dev Biol. 2012. PMID: 22484611 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials