Cited by 480T-cell and B-cell ImmunologyTGF-β signaling in diseasesPsoriasis: Treatment and Pathogenesis

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Cellular Mechanisms of Fatal Early-Onset Autoimmunity in Mice with the T Cell-Specific Targeting of Transforming Growth Factor-β Receptor

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Marie, Julien C., Liggitt, Denny, Rudensky, Alexander Y.·2006·Immunity

DOI 10.1016/j.immuni.2006.07.012

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Abstract

Transforming growth factor-beta (TGF-beta) has been implicated in the control of differentiation and proliferation of multiple cell types. However, a role for TGF-beta in the control of immune homeostasis is not fully understood because of its pleiotropic action. Here we report that complete ablation of the TGF-beta signaling in T cells engendered aggressive early-onset, multiorgan, autoimmune-associated lesions with 100% mortality. Peripheral CD4+ and CD8+ T cells with TGF-beta-receptor II (TGF-betaRII) deficiency activated cytolytic and T helper 1 (Th1) differentiation program in a cell-intrinsic T cell receptor (TCR)-specific fashion. Furthermore, TGF-betaRII deficiency blocked the development of canonical CD1d-restricted NKT cells. Instead, it facilitated generation of a highly pathogenic T cell subset exhibiting multiple hallmarks of NK cells and sharply elevated amounts of FasL, perforin, granzymes, and interferon-gamma. Thus, TGF-beta signaling in peripheral T cells is crucial in restraining TCR activation-dependent Th1, cytotoxic, and NK cell-like differentiation program which, when left unchecked, leads to rapidly progressing fatal autoimmunity.

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Authors: Marie, J. C., Liggitt, D., & Rudensky, A. Y.
Affiliations: Howard Hughes Medical Institute (US)
University of Washington (US)
Corresponding author: Marie, Julien C.
Rudensky, Alexander Y.
ORCID: Marie, Julien C.
Liggitt, Denny
Rudensky, Alexander Y.
Venue: Immunity
Publisher: Elsevier BV
Published: 2006-09
Volume: 25
Issue: 3
Pages: 441-454
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/j.immuni.2006.07.012
OpenAlex: W2055061339
Cited by: 480
References: 43
Citations by year: 2026: 7 · 2025: 12 · 2024: 17 · 2023: 23 · 2022: 22 · 2021: 25 · 2020: 14 · 2019: 17 · 2018: 25 · 2017: 24 · 2016: 25 · 2015: 20 · 2014: 23 · 2013: 27 · 2012: 32
FWCI: 13.28
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2511 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
Keywords: TGF-beta signaling, TGFBR2, autoimmunity, Th1 differentiation, cytotoxic T lymphocytes, NKT cells, immune homeostasis, T cell receptor stimulation, CD4+ T cells, CD8+ T cells, perforin, granzymes, interferon-gamma, Fas ligand
MeSH terms: Animals, Antigens, Surface, Autoimmune Diseases, Cells, Cultured, Immune Tolerance, Lymphocyte Depletion, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, Time Factors, Receptors, Transforming Growth Factor beta, Mice, Knockout, Lectins, C-Type, Mice, NK Cell Lectin-Like Receptor Subfamily B

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Cellular Mechanisms of Fatal Early-Onset Autoimmunity in Mice with the T Cell-Specific Targeting of Transforming Growth Factor-β Receptor

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