T cell apoptosis by tryptophan catabolism

Fallarino, F; Grohmann, U; Vacca, C; Bianchi, R; Orabona, C; Spreca, A; Fioretti, M C; Puccetti, P

doi:10.1038/sj.cdd.4401073

Cited by 1,022Tryptophan and brain disordersT-cell and B-cell ImmunologyReproductive System and Pregnancy

T cell apoptosis by tryptophan catabolism

Fallarino, F, Grohmann, U, Vacca, C, Bianchi, R, Orabona, C, Spreca, A, Fioretti, M C, Puccetti, P·2002·Cell Death & Differentiation

DOI 10.1038/sj.cdd.4401073

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Abstract

Indoleamine 2,3-dioxygenase (IDO) is a tryptophan-catabolizing enzyme that, expressed by different cell types, has regulatory effects on T cells resulting from tryptophan depletion in specific local tissue microenvironments. Different mechanisms, however, might contribute to IDO-dependent immune regulation. We show here that tryptophan metabolites in the kynurenine pathway, such as 3-hydroxyanthranilic and quinolinic acids, will induce the selective apoptosis in vitro of murine thymocytes and of Th1 but not Th2 cells. T cell apoptosis was observed at relatively low concentrations of kynurenines, did not require Fas/Fas ligand interactions, and was associated with the activation of caspase-8 and the release of cytochrome c from mitochondria. When administered in vivo, the two kynurenines caused depletion of specific thymocyte subsets in a fashion qualitatively similar to dexamethasone. These data suggest that the selective deletion of T lymphocytes may be a major mechanism whereby tryptophan metabolism affects immunity under physiopathologic conditions.

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Authors: Fallarino, F., Grohmann, U., Vacca, C., Bianchi, R., Orabona, C., Spreca, A., Fioretti, M. C., & Puccetti, P.
Affiliations: University of Perugia (IT)
Corresponding author: Puccetti, P
ORCID: Fallarino, F
Grohmann, U
Vacca, C
Bianchi, R
Orabona, C
Puccetti, P
Venue: Cell Death & Differentiation
Publisher: Springer Science and Business Media LLC
Published: 2002-10
Volume: 9
Issue: 10
Pages: 1069-1077
ISSN: 1350-9047 (ISSN-L)
1476-5403
DOI: 10.1038/sj.cdd.4401073
OpenAlex: W2072078248
Cited by: 1,022
References: 52
Citations by year: 2026: 27 · 2025: 38 · 2024: 54 · 2023: 58 · 2022: 67 · 2021: 72 · 2020: 68 · 2019: 51 · 2018: 40 · 2017: 40 · 2016: 40 · 2015: 56 · 2014: 41 · 2013: 37 · 2012: 31
FWCI: 9.16
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Cell Death and Differentiation (publishedVersion)
PubMed (publishedVersion)
Funders: Associazione Italiana per la Ricerca sul Cancro
Fondazione Italiana per la Ricerca sul Cancro
Topics: Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords: tryptophan catabolism, indoleamine 2,3-dioxygenase, kynurenine pathway, T cell apoptosis, thymocytes, Th1 cells, Th2 cells, 3-hydroxyanthranilic acid, quinolinic acid, caspase-8, cytochrome c release, thymocyte depletion, immune regulation, tryptophan metabolism
MeSH terms: Animals, Autoimmune Diseases, Cell Nucleus, Cells, Cultured, Cytochrome c Group, Cytosol, Dose-Response Relationship, Drug, Kynurenine, Mice, Inbred C57BL, Mice, Inbred DBA, Microscopy, Electron, Mitochondria, T-Lymphocytes, Thymus Gland, Tryptophan, 3-Hydroxyanthranilic Acid, Apoptosis, Quinolinic Acid, Self Tolerance, Th1 Cells, fas Receptor, Caspases, Mice, Caspase 8, Caspase 9, Caspase Inhibitors

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T cell apoptosis by tryptophan catabolism

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