Suppression of T-cell responsiveness by inducible cAMP early repressor (ICER)

Autor: Josef Bodor, Lionel Feigenbaum, Jana Bodorova, Marvin S. Reitz, Cathy Bare, Ronald E. Gress
Rok vydání: 2001
Předmět:
Chemokine
CAMP-Responsive Element Modulator
Transcription
Genetic
medicine.medical_treatment
T cell
Immunology
Repressor
Mice
Transgenic
Lymphocyte Activation
Second Messenger Systems
Dinoprostone
Cyclic AMP Response Element Modulator
Interferon-gamma
Mice
Th2 Cells
Interferon
Cyclic AMP
medicine
Animals
Humans
Immunology and Allergy
Transcriptional attenuation
Promoter Regions
Genetic
education
Macrophage inflammatory protein
Mice
Inbred BALB C
education.field_of_study
biology
Ionomycin
Colforsin
Cell Biology
Th1 Cells
Molecular biology
DNA-Binding Proteins
Mice
Inbred C57BL
Repressor Proteins
Cytokine
medicine.anatomical_structure
Gene Expression Regulation
biology.protein
Cytokines
Interleukin-2
Tetradecanoylphorbol Acetate
Chemokines
Lymphocyte Culture Test
Mixed
Cell Division
Spleen
medicine.drug
Zdroj: Journal of Leukocyte Biology. 69:1053-1059
ISSN: 1938-3673
0741-5400
DOI: 10.1189/jlb.69.6.1053
Popis: Depending on the nature of the costimulation of T lymphocytes, expression of regulatory cytokines and chemokines is either susceptibleor resistant to cyclic AMP (cAMP)-mediated inhibition. Our data showthat cAMP-mediated inhibition of endogenously expressed cytokines, which is characteristic for T helper (Th) 1- and Th 2-like phenotypes, correlates with the induction of a potent transcriptional repressor, inducible cAMP early repressor (ICER), in both subsets of T cellsactivated under conditions of suboptimal interleukin-2 (IL-2)expression. Importantly, Th-specific expression of certain chemokinesis also susceptible to cAMP-mediated transcriptional attenuation. Todetermine whether ICER per se, rather than forskolin-mediated elevationof intracellular cAMP, is responsible for the observed inhibitoryeffect, we generated transgenic mice expressing ICER under the controlof a lymphocyte-specific lck promoter. On stimulation, transgenic thymocytes overexpressing ICER exhibited reduced levels of IL-2 and interferon (IFN)-γ and failed to express the macrophageinflammatory protein (MIP)-1α and MIP-1β genes. Splenic T cellsfrom ICER-transgenic mice showed a defect in proliferation and lacked amixed lymphocyte reaction response, implying that ICER-mediatedinhibition of cytokine and chemokine expression might play an importantrole in T-cell inactivation.
Databáze: OpenAIRE
Externí odkaz: