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A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
Nuclear factor (NF)-kappaB-dependent thyroid hormone receptor beta1 expression controls dendritic cell function via
Iván D Mascanfroni1, María Del Mar Montesinos1, Vanina A Alamino1
1Centro de Investigaciones en Bioquímica Clínica e Inmunología, Consejo Nacional de Investigaciones Científicas y Técnicas, Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba.
The Journal of Biological Chemistry
|December 19, 2009
Summary
Thyroid hormone receptor beta(1) signaling regulates dendritic cell maturation and IL-12 production via an Akt-dependent pathway. This study reveals a novel autocrine loop controlling hormone-dependent immune responses.
Area of Science:
- Immunology
- Endocrinology
- Molecular Biology
Background:
- The interaction between the immune and endocrine systems is complex.
- The specific role of thyroid hormones in adaptive immunity remains unclear.
- Dendritic cells (DCs) are key regulators of adaptive immunity.
Purpose of the Study:
- To investigate the role of thyroid hormone receptor (TR) beta(1) signaling in dendritic cell (DC) function.
- To elucidate the intracellular mechanisms of TR beta(1)-mediated immunomodulation.
- To explore potential autocrine regulatory loops in thyroid hormone signaling within DCs.
Main Methods:
- Exposure of DCs to triiodothyronine (T(3)) and assessment of Akt phosphorylation.
- Use of small interfering RNA (siRNA) to silence TR beta(1) expression.
- Analysis of DC maturation, IL-12 production, and NF-kappaB pathway activation.
- Chromatin immunoprecipitation (ChIP) to identify regulatory elements in the TRB1 gene promoter.
Main Results:
- T(3) exposure increased Akt phosphorylation in DCs, promoting maturation and IL-12 production.
- TR beta(1) signaling was essential for T(3)-induced DC maturation, IL-12 secretion, Akt activation, and I kappaB-epsilon degradation.
- T(3) up-regulated TR beta(1) expression via an NF-kappaB-dependent mechanism, indicating an autocrine loop.
- A novel NF-kappaB consensus site was identified in the TRB1 gene promoter.
Conclusions:
- Thyroid hormone receptor beta(1) signaling is a critical regulator of dendritic cell maturation and function.
- A T(3)-induced, NF-kappaB-dependent mechanism controls TR beta(1) expression, creating an autocrine loop.
- TR beta(1) signaling promotes DC maturation and IL-12 production through an Akt-dependent, PI3K-independent pathway.
- These findings highlight a novel cross-talk between the immune and endocrine systems with implications for immunopathology.
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