Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype.

Geiser, A G; Letterio, J J; Kulkarni, A B; Karlsson, S; Roberts, A B; Sporn, M B

doi:10.1073/pnas.90.21.9944

Cited by 179TGF-β signaling in diseasesT-cell and B-cell ImmunologyReproductive System and Pregnancy

Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype.

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Geiser, A G, Letterio, J J, Kulkarni, A B, Karlsson, S, Roberts, A B, Sporn, M B·1993·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.90.21.9944PMC PMC47689

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Abstract

The phenotype of the transforming growth factor beta 1 (TGF-beta 1) null mouse has been previously described and is characterized by inflammatory infiltrates in multiple organs leading to a wasting syndrome and death as early as 3 weeks after birth. Since this phenotype occurs in the absence of any detectable pathogen, potential autoimmune disease mechanisms were investigated. We examined major histocompatibility complex (MHC) mRNA expression in tissues of the TGF-beta 1 null mouse and found levels of both the class I and class II MHC mRNA elevated compared to normal or TGF-beta 1 heterozygous littermates. This elevated expression was seen prior to any evidence of inflammatory infiltrates, suggesting a causal relationship between increased MHC expression and activation of immune cell populations. Cell surface expression of MHC molecules was detected by immunohistochemistry and correlated well with mRNA levels. Expression of mRNA for interferon gamma and its receptor was unchanged at the ages when increased MHC expression became apparent. Down-regulation of class I MHC expression by TGF-beta 1 was also demonstrated in vitro in fibroblasts isolated from TGF-beta 1 null mice. These findings suggest that one natural function of TGF-beta 1 is to control expression of both MHC classes. Altered regulation of MHC expression may be a critical step leading to the multifocal inflammation and wasting syndrome seen in the TGF-beta 1 null mouse. These results suggest potential applications for TGF-beta in the management of autoimmune disease, allograft rejection, and other problems associated with altered MHC expression.

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Authors: Geiser, A. G., Letterio, J. J., Kulkarni, A. B., Karlsson, S., Roberts, A. B., & Sporn, M. B.
Affiliations: National Institutes of Health (US)
ORCID: Letterio, J J
Karlsson, S
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1993-11
Volume: 90
Issue: 21
Pages: 9944-9948
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.90.21.9944
PMC: PMC47689
OpenAlex: W2061403592
Cited by: 179
References: 49
Citations by year: 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 1 · 2017: 4 · 2016: 1 · 2015: 2 · 2013: 1 · 2012: 2
FWCI: 3.35
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Keywords: TGF-β1, major histocompatibility complex, MHC class I, MHC class II, autoimmune disease, interferon-gamma, cachexia, postnatal development, allograft rejection, fibroblasts
MeSH terms: Interferon gamma Receptor, Animals, Base Sequence, Cells, Cultured, Fibroblasts, Gene Expression Regulation, Interferon-gamma, Major Histocompatibility Complex, Mice, Mutant Strains, Molecular Sequence Data, Organ Specificity, Phenotype, RNA, Messenger, Skin, Polymerase Chain Reaction, Transforming Growth Factor beta, Receptors, Interferon, DNA Primers, Mice

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Transforming growth factor beta 1 (TGF-beta 1) controls expression of major histocompatibility genes in the postnatal mouse: aberrant histocompatibility antigen expression in the pathogenesis of the TGF-beta 1 null mouse phenotype.

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