Abstract
Previously, we have shown in a model of hypersensitivity pneumonitis that Th1-biased C57BL/6 mice are susceptible and Th2-biased DBA/2 mice are resistant to disease. We also showed that this was explained in part by differential regulation of IL-12 by IL-4. For these reasons, we postulated that C57BL/6 and DBA/2 mice differentially express IL-4. In this study, we show that C57BL/6 immune cells express Th2 but not Th1 cytokines at lower levels than DBA/2 cells. We also found that C57BL/6 splenocytes exhibit decreased mRNA stability of Th2 cytokines, relative to DBA/2 splenocytes. Stability of IL-2 and IFN-gamma were similar in the two strains of mice. Differences in Th2 cytokine mRNA stability between C57BL/6 and DBA/2 cells were not due to sequence polymorphism at specific regions of the IL-4/IL-13 locus. Furthermore, expression of Th1- and Th2-specific transcription factors T-bet and GATA-3, as well as the nuclear factor of activated T cells transcription factor, NFATc, was not significantly different between the two mice. Our data suggest that decreased mRNA stability of Th2 cytokines in C57BL/6 splenocytes may underlie the differential susceptibility to hypersensitivity pneumonitis between C57BL/6 and DBA/2 mice. Moreover, our results indicate that regulation of mRNA stability may serve as an important mechanism underlying Th1/Th2 immune polarization.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alveolitis, Extrinsic Allergic / immunology*
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Alveolitis, Extrinsic Allergic / metabolism
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Animals
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Base Sequence / genetics
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism
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Disease Susceptibility / immunology
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Female
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GATA3 Transcription Factor
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Genetic Markers / immunology
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Immunophenotyping
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Interleukin-4 / biosynthesis
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Interleukin-4 / genetics*
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Interleukin-4 / metabolism
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Interleukin-4 / pharmacology
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Kinetics
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Lung / cytology
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Lung / immunology
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Lung / metabolism
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Lymphocyte Count
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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NFATC Transcription Factors
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Nuclear Proteins*
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Polymorphism, Genetic / immunology
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RNA Stability / immunology*
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RNA, Messenger / metabolism*
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Box Domain Proteins
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Th1 Cells / cytology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Th2 Cells / cytology
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Th2 Cells / immunology*
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Th2 Cells / metabolism
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Trans-Activators / biosynthesis
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Trans-Activators / metabolism
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Transcription Factors / biosynthesis
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Transcription Factors / metabolism
Substances
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DNA-Binding Proteins
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GATA3 Transcription Factor
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Gata3 protein, mouse
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Genetic Markers
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NFATC Transcription Factors
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Nuclear Proteins
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RNA, Messenger
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Trans-Activators
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Transcription Factors
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Interleukin-4